Sample records for t-test revealed significant

  1. Coagulation tests show significant differences in patients with breast cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Duranyildiz, Derya

    2014-06-01

    Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation assays for various clinicopathologic factors in breast cancer patients. A total of 123 female breast cancer patients were enrolled into the study. All the patients were treatment naïve. Pretreatment blood coagulation tests including PT, APTT, PTA, INR, D-dimer, fibrinogen levels, and platelet counts were evaluated. Median age of diagnosis was 51 years old (range 26-82). Twenty-two percent of the group consisted of metastatic breast cancer patients. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group except for PT (p<0.001 for all variables except for PT; p=0.08). Elderly age (>50 years) was associated with higher D-dimer levels (p=0.003). Metastatic patients exhibited significantly higher D-dimer values when compared with early breast cancer patients (p=0.049). Advanced tumor stage (T3 and T4) was associated with higher INR (p=0.05) and lower PTA (p=0.025). In conclusion, coagulation tests show significant differences in patients with breast cancer.

  2. 40 CFR Appendix IV to Part 265 - Tests for Significance

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... changes in the concentration or value of an indicator parameter in periodic ground-water samples when... then be compared to the value of the t-statistic found in a table for t-test of significance at the specified level of significance. A calculated value of t which exceeds the value of t found in the table...

  3. 40 CFR Appendix IV to Part 265 - Tests for Significance

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... changes in the concentration or value of an indicator parameter in periodic ground-water samples when... then be compared to the value of the t-statistic found in a table for t-test of significance at the specified level of significance. A calculated value of t which exceeds the value of t found in the table...

  4. 40 CFR Appendix IV to Part 265 - Tests for Significance

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... changes in the concentration or value of an indicator parameter in periodic ground-water samples when... then be compared to the value of the t-statistic found in a table for t-test of significance at the specified level of significance. A calculated value of t which exceeds the value of t found in the table...

  5. 40 CFR Appendix IV to Part 265 - Tests for Significance

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... changes in the concentration or value of an indicator parameter in periodic ground-water samples when... then be compared to the value of the t-statistic found in a table for t-test of significance at the specified level of significance. A calculated value of t which exceeds the value of t found in the table...

  6. Significance of Landsat-7 Spacecraft Level Thermal Balance and Thermal Test for ETM+Instrument

    NASA Technical Reports Server (NTRS)

    Choi, Michael K.

    1999-01-01

    The thermal design and the instrument thermal vacuum (T/V) test of the Landsat-7 Enhanced Thematic Mapper Plus (ETM+) instrument were based on the Landsat-4, 5 and 6 heritage. The ETM+ scanner thermal model was also inherited from Landsat-4, 5 and 6. The temperature predictions of many scanner components in the original thermal model had poor agreement with the spacecraft and instrument integrated sun-pointing safehold (SPSH) thermal balance (T/B) test results. The spacecraft and instrument integrated T/B test led to a change of the Full Aperture Calibrator (FAC) motor stack "solar shield" coating from MIL-C-5541 to multi-layer insulation (MLI) thermal blanket. The temperature predictions of the Auxiliary Electronics Module (AEM) in the thermal model also had poor agreement with the T/B test results. Modifications to the scanner and AEM thermal models were performed to give good agreement between the temperature predictions and the test results. The correlated ETM+ thermal model was used to obtain flight temperature predictions. The flight temperature predictions in the nominal 15-orbit mission profile, plus margins, were used as the yellow limits for most of the ETM+ components. The spacecraft and instrument integrated T/B and TN test also revealed that the standby heater capacity on the Scan Mirror Assembly (SMA) was insufficient when the Earth Background Simulator (EBS) was 1 50C or colder, and the baffle heater possibly caused the coherent noise in the narrow band data when it was on. Also, the cooler cool-down was significantly faster than that in the instrument T/V test, and the coldest Cold Focal Plane Array (CFPA) temperature achieved was colder.

  7. When "t"-Tests or Wilcoxon-Mann-Whitney Tests Won't Do

    ERIC Educational Resources Information Center

    McElduff, Fiona; Cortina-Borja, Mario; Chan, Shun-Kai; Wade, Angie

    2010-01-01

    "t"-Tests are widely used by researchers to compare the average values of a numeric outcome between two groups. If there are doubts about the suitability of the data for the requirements of a "t"-test, most notably the distribution being non-normal, the Wilcoxon-Mann-Whitney test may be used instead. However, although often…

  8. T-2 mycotoxin treatment of newborn rat pups does not significantly affect nervous system functions in adulthood.

    PubMed

    Varró, Petra; Béldi, Melinda; Kovács, Melinda; Világi, Ildikó

    2018-03-01

    T-2 toxin is primarily produced by Fusarium sp. abundant under temperate climatic conditions. Its main harmful effect is the inhibition of protein synthesis. Causing oxidative stress, it also promotes lipid peroxidation and changes plasma membrane phospholipid composition; this may lead to nervous system alterations. The aim of the present study was to examine whether a single dose of T-2 toxin administered at newborn age has any long-lasting effects on nervous system functions. Rat pups were treated on the first postnatal day with a single intraperitoneal dose of T-2 toxin (0.2 mg/bwkg). Body weight of treated pups was lower during the second and third week of life, compared to littermates; later, weight gain was recovered. At young adulthood, behavior was tested in the open field, and no difference was observed between treated and control rats. Field potential recordings from somatosensory cortex and hippocampus slices did not reveal any significant difference in neuronal network functions. In case of neocortical field EPSP, the shape was slightly different in treated pups. Long-term synaptic plasticity was also comparable in both groups. Seizure susceptibility of the slices was not different, either. In conclusion, T-2 toxin did not significantly affect basic nervous system functions at this dose.

  9. [CLINICAL UTILITY OF T-SPOT.TB ASSAY WITH T-Cell Xtend REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS IN THE FIELD TEST AT OUR HOSPITAL].

    PubMed

    Nemoto, Kenji; Oh-ishi, Shuji; Taguchi, Masato; Hyodo, Kentaro; Kanazawa, Jun; Miura, Yukiko; Takaku, Takio; Usui, Shingo; Hayashihara, Kenji; Saito, Takefumi

    2016-04-01

    T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.

  10. The Dichotic Digits difference Test (DDdT): Development, Normative Data, and Test-Retest Reliability Studies Part 1.

    PubMed

    Cameron, Sharon; Glyde, Helen; Dillon, Harvey; Whitfield, Jessica; Seymour, John

    2016-06-01

    The dichotic digits test is one of the most widely used assessment tools for central auditory processing disorder. However, questions remain concerning the impact of cognitive factors on test results. To develop the Dichotic Digits difference Test (DDdT), an assessment tool that could differentiate children with cognitive deficits from children with genuine dichotic deficits based on differential test results. The DDdT consists of four subtests: dichotic free recall (FR), dichotic directed left ear (DLE), dichotic directed right ear (DRE), and diotic. Scores for six conditions are calculated (FR left ear [LE], FR right ear [RE], and FR total, as well as DLE, DRE, and diotic). Scores for four difference measures are also calculated: dichotic advantage, right-ear advantage (REA) FR, REA directed, and attention advantage. Experiment 1 involved development of the DDdT, including error rate analysis. Experiment 2 involved collection of normative and test-retest reliability data. Twenty adults (aged 25 yr 10 mo to 50 yr 7 mo, mean 36 yr 4 mo) took part in the development study; 62 normal-hearing, typically developing, primary-school children (aged 7 yr 1 mo to 11 yr 11 mo, mean 9 yr 4 mo) and 10 adults (aged 25 yr 0 mo to 51 yr 6 mo, mean 34 yr 10 mo) took part in the normative and test-retest reliability study. In Experiment 1, error rate analysis was conducted on the 36 digit-pair combinations of the DDdT. Normative data collected in Experiment 2 were arcsine transformed to achieve a distribution that was closer to a normal distribution and z-scores calculated. Pearson product-moment correlations were used to determine the strength of relationships between DDdT conditions. The development study revealed no significant differences in the adult population between test and retest on any DDdT condition. Error rates on 36 digit pairs ranged from 1.5% to 16.7%. The most and the least error-prone digits were removed before commencement of the normative data study, leaving 25

  11. Overview of T.E.S.T. (Toxicity Estimation Software Tool)

    EPA Science Inventory

    This talk provides an overview of T.E.S.T. (Toxicity Estimation Software Tool). T.E.S.T. predicts toxicity values and physical properties using a variety of different QSAR (quantitative structure activity relationship) approaches including hierarchical clustering, group contribut...

  12. Test – Retest Reliability and Concurrent Validity of in vivo Myelin Content Indices: Myelin Water Fraction and Calibrated T1w/T2w Image Ratio

    PubMed Central

    Arshad, Muzamil; Stanley, Jeffrey A.; Raz, Naftali

    2016-01-01

    In an age-heterogeneous sample of healthy adults, we examined test-retest reliability (with and without participant re-positioning) of two popular MRI methods of estimating myelin content: modeling the short spin-spin (T2) relaxation component of multi-echo imaging data and computing the ratio of T1-weighted and T2-weighted images (T1w/T2w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi-component T2 relaxation data as a standard, we evaluate the concurrent and differential validity of T1w/T2w ratio images. The results revealed high reliability of MWF and T1w/T2w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T1w/T2w ratio in only two of six examined regions of the cerebral white matter. Notably, significant correlations of the same or greater magnitude were observed for T1w/T2w ratio and the intermediate T2 relaxation time constant, which is believed to reflect differences in the mobility of water between the intracellular and extracellular compartments. We conclude that although both methods are highly reliable and thus well-suited for longitudinal studies, T1w/T2w ratio has low criterion validity and may be not an optimal index of subcortical myelin content. PMID:28009069

  13. Reveal Salmonella 2.0 test for detection of Salmonella spp. in foods and environmental samples. Performance Tested Method 960801.

    PubMed

    Hoerner, Rebecca; Feldpausch, Jill; Gray, R Lucas; Curry, Stephanie; Islam, Zahidul; Goldy, Tim; Klein, Frank; Tadese, Theodros; Rice, Jennifer; Mozola, Mark

    2011-01-01

    Reveal Salmonella 2.0 is an improved version of the original Reveal Salmonella lateral flow immunoassay and is applicable to the detection of Salmonella enterica serogroups A-E in a variety of food and environmental samples. A Performance Tested Method validation study was conducted to compare performance of the Reveal 2.0 method with that of the U.S. Department of Agriculture-Food Safety and Inspection Service or U.S. Food and Drug Administration/Bacteriological Analytical Manual reference culture methods for detection of Salmonella spp. in chicken carcass rinse, raw ground turkey, raw ground beef, hot dogs, raw shrimp, a ready-to-eat meal product, dry pet food, ice cream, spinach, cantaloupe, peanut butter, stainless steel surface, and sprout irrigation water. In a total of 17 trials performed internally and four trials performed in an independent laboratory, there were no statistically significant differences in performance of the Reveal 2.0 and reference culture procedures as determined by Chi-square analysis, with the exception of one trial with stainless steel surface and one trial with sprout irrigation water where there were significantly more positive results by the Reveal 2.0 method. Considering all data generated in testing food samples using enrichment procedures specifically designed for the Reveal method, overall sensitivity of the Reveal method relative to the reference culture methods was 99%. In testing environmental samples, sensitivity of the Reveal method relative to the reference culture method was 164%. For select foods, use of the Reveal test in conjunction with reference method enrichment resulted in overall sensitivity of 92%. There were no unconfirmed positive results on uninoculated control samples in any trials for specificity of 100%. In inclusivity testing, 102 different Salmonella serovars belonging to serogroups A-E were tested and 99 were consistently positive in the Reveal test. In exclusivity testing of 33 strains of non

  14. Test-retest reliability and concurrent validity of in vivo myelin content indices: Myelin water fraction and calibrated T1 w/T2 w image ratio.

    PubMed

    Arshad, Muzamil; Stanley, Jeffrey A; Raz, Naftali

    2017-04-01

    In an age-heterogeneous sample of healthy adults, we examined test-retest reliability (with and without participant repositioning) of two popular MRI methods of estimating myelin content: modeling the short spin-spin (T 2 ) relaxation component of multi-echo imaging data and computing the ratio of T 1 -weighted and T 2 -weighted images (T 1 w/T 2 w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi-component T 2 relaxation data as a standard, we evaluate the concurrent and differential validity of T 1 w/T 2 w ratio images. The results revealed high reliability of MWF and T 1 w/T 2 w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T 1 w/T 2 w ratio in only two of six examined regions of the cerebral white matter. Notably, significant correlations of the same or greater magnitude were observed for T 1 w/T 2 w ratio and the intermediate T 2 relaxation time constant, which is believed to reflect differences in the mobility of water between the intracellular and extracellular compartments. We conclude that although both methods are highly reliable and thus well-suited for longitudinal studies, T 1 w/T 2 w ratio has low criterion validity and may be not an optimal index of subcortical myelin content. Hum Brain Mapp 38:1780-1790, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Detecting differentially expressed genes in heterogeneous diseases using half Student's t-test.

    PubMed

    Hsu, Chun-Lun; Lee, Wen-Chung

    2010-12-01

    Microarray technology provides information about hundreds and thousands of gene-expression data in a single experiment. To search for disease-related genes, researchers test for those genes that are differentially expressed between the case subjects and the control subjects. The authors propose a new test, the 'half Student's t-test', specifically for detecting differentially expressed genes in heterogeneous diseases. Monte-Carlo simulation shows that the test maintains the nominal α level quite well for both normal and non-normal distributions. Power of the half Student's t is higher than that of the conventional 'pooled' Student's t when there is heterogeneity in the disease under study. The power gain by using the half Student's t can reach ∼10% when the standard deviation of the case group is 50% larger than that of the control group. Application to a colon cancer data reveals that when the false discovery rate (FDR) is controlled at 0.05, the half Student's t can detect 344 differentially expressed genes, whereas the pooled Student's t can detect only 65 genes. Or alternatively, if only 50 genes are to be selected, the FDR for the pooled Student's t has to be set at 0.0320 (false positive rate of ∼3%), but for the half Student's t, it can be at as low as 0.0001 (false positive rate of about one per ten thousands). The half Student's t-test is to be recommended for the detection of differentially expressed genes in heterogeneous diseases.

  16. Color discrimination testing reveals early printshop solvent neurotoxicity better than a neuropsychological test battery.

    PubMed

    Braun, C M; Daigneault, S; Gilbert, B

    1989-01-01

    Twenty standardized neuropsychological tests were compared to the Lanthony D-15 desaturated panel test of chromotopsia to determine which measures would most effectively discriminate solvent-exposed print workers from controls. All the workers of the printing services of Université du Québec a Montréal (N = 29) were assessed excepted one who refused to participate. Twenty-nine workers (employed on a full time basis) matched for occupation, age, sex, education, vocabulary, and written arithmetic (p >.13) with the print workers served as controls. Air samples revealed exposure to ethanol, perchloroethylene, methyl chloride, xylene, toluene, and stoddard solvent in the print shop. None of the 20 neuropsychological measures yielded a statistically significant decrement in the print workers. On the other hand, the Lanthony D-15 test revealed a significant group difference (p <.01) and a highly significant interaction between job category within the print shop and dyschromatopsia (p <.001) - the graphists, photocopiers, and printers/binders manifesting increasing severity of impairment as a function of increasing magnitude, and/or type, of dose. The results were interpreted to mean that in a cohort of printers with low seniority (10.42 years) such as this one, neuro-opthalmotoxic effects can be observed earlier than putative neuropsychotoxic effects with the tools at hand.

  17. Reveal Listeria 2.0 test for detection of Listeria spp. in foods and environmental samples.

    PubMed

    Alles, Susan; Curry, Stephanie; Almy, David; Jagadeesan, Balamurugan; Rice, Jennifer; Mozola, Mark

    2012-01-01

    A Performance Tested Method validation study was conducted for a new lateral flow immunoassay (Reveal Listeria 2.0) for detection of Listeria spp. in foods and environmental samples. Results of inclusivity testing showed that the test detects all species of Listeria, with the exception of L. grayi. In exclusivity testing conducted under nonselective growth conditions, all non-listeriae tested produced negative Reveal assay results, except for three strains of Lactobacillus spp. However, these lactobacilli are inhibited by the selective Listeria Enrichment Single Step broth enrichment medium used with the Reveal method. Six foods were tested in parallel by the Reveal method and the U.S. Food and Drug Administration/Bacteriological Analytical Manual (FDA/BAM) reference culture procedure. Considering data from both internal and independent laboratory trials, overall sensitivity of the Reveal method relative to that of the FDA/BAM procedure was 101%. Four foods were tested in parallel by the Reveal method and the U.S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS) reference culture procedure. Overall sensitivity of the Reveal method relative to that of the USDA-FSIS procedure was 98.2%. There were no statistically significant differences in the number of positives obtained by the Reveal and reference culture procedures in any food trials. In testing of swab or sponge samples from four types of environmental surfaces, sensitivity of Reveal relative to that of the USDA-FSIS reference culture procedure was 127%. For two surface types, differences in the number of positives obtained by the Reveal and reference methods were statistically significant, with more positives by the Reveal method in both cases. Specificity of the Reveal assay was 100%, as there were no unconfirmed positive results obtained in any phase of the testing. Results of ruggedness experiments showed that the Reveal assay is tolerant of modest deviations in test sample volume and

  18. Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis.

    PubMed

    Imburgio, Michael J; Orr, Joseph M

    2018-05-01

    A meta-analysis of studies using single-session transcranial direct current stimulation (tDCS) to target the dorsolateral prefrontal cortex (DLPFC) was undertaken to examine the effect of stimulation on executive function (EF) in healthy samples. 27 studies were included in analyses, yielding 71 effect sizes. The most relevant measure for each task was determined a priori and used to calculate Hedge's g. Methodological characteristics of each study were examined individually as potential moderators of effect size. Stimulation effects on three domains of EF (inhibition of prepotent responses, mental set shifting, and information updating and monitoring) were analyzed separately. In line with previous work, the current study found no significant effect of anodal unilateral tDCS, cathodal unilateral tDCS, or bilateral tDCS on EF. Further moderator and subgroup analyses were only carried out for anodal unilateral montages due to the small number of studies using other montages. Subgroup analyses revealed a significant effect of anodal unilateral tDCS on updating tasks, but not on inhibition or set-shifting tasks. Cathode location significantly moderated the effect of anodal unilateral tDCS. Extracranial cathodes yielded a significant effect on EF while cranial cathodes yielded no effect. Anode size also significantly moderated effect of anodal unilateral tDCS, with smaller anodes being more effective than larger anodes. In summary, anodal DLPFC stimulation is more effective at improving updating ability than inhibition and set-shifting ability, but anodal stimulation can significantly improve general executive function when extracranial cathodes or small anodes are used. Future meta-analyses may examine how stimulation's effects on specific behavioral tasks, rather than broader domains, might be affected by methodological moderators. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria

    PubMed Central

    Mukai, Takahito; Reynolds, Noah M.; Crnković, Ana; Söll, Dieter

    2017-01-01

    The tRNA identity elements for some amino acids are distinct between the bacterial and archaeal domains. Searching in recent genomic and metagenomic sequence data, we found some candidate phyla radiation (CPR) bacteria with archaeal tRNA identity for Tyr-tRNA and Trp-tRNA synthesis. These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS) predicted to be derived from DPANN superphylum archaea, while the cognate tRNATyr and tRNATrp genes reveal bacterial or archaeal origins. We identified a trace of domain fusion and swapping in the archaeal-type TyrRS gene of a bacterial lineage, suggesting that CPR bacteria may have used this mechanism to create diverse proteins. Archaeal-type TrpRS of bacteria and a few TrpRS species of DPANN archaea represent a new phylogenetic clade (named TrpRS-A). The TrpRS-A open reading frames (ORFs) are always associated with another ORF (named ORF1) encoding an unknown protein without global sequence identity to any known protein. However, our protein structure prediction identified a putative HIGH-motif and KMSKS-motif as well as many α-helices that are characteristic of class I aminoacyl-tRNA synthetase (aaRS) homologs. These results provide another example of the diversity of molecular components that implement the genetic code and provide a clue to the early evolution of life and the genetic code. PMID:28230768

  20. Thou Shalt Not Bear False Witness against Null Hypothesis Significance Testing

    ERIC Educational Resources Information Center

    García-Pérez, Miguel A.

    2017-01-01

    Null hypothesis significance testing (NHST) has been the subject of debate for decades and alternative approaches to data analysis have been proposed. This article addresses this debate from the perspective of scientific inquiry and inference. Inference is an inverse problem and application of statistical methods cannot reveal whether effects…

  1. Creep, creep-rupture tests of Al-surface-alloyed T91 steel in liquid lead bismuth at 500 and 550 °C

    NASA Astrophysics Data System (ADS)

    Weisenburger, A.; Jianu, A.; An, W.; Fetzer, R.; Del Giacco, Mattia; Heinzel, A.; Müller, G.; Markov, V. G.; Kasthanov, A. D.

    2012-12-01

    Surface layers made of FeCrAl alloys on T91 steel have shown their capability as corrosion protection barriers in lead bismuth. Pulsed electron beam treatment improves the density and more over the adherence of such layers. After the treatment of previously deposited coatings a surface graded material is achieved with a metallic bonded interface. Creep-rupture tests of T91 in lead-alloy at 550 °C reveal significant reduced creep strength of non-modified T91 test specimens. Oxide scales protecting the steels from attacks of the liquid metal will crack at a certain strain leading to a direct contact between the steel and the liquid metal. The negative influence of the lead-alloy on the creep behavior of non-modified T91 is stress dependent, but below a threshold stress value of 120 MPa at 550 °C this influence becomes almost negligible. At 500 °C and stress values of 200 MPa and 220 MPa the creep rates are comparable between them and significantly lower than creep rates at 180 MPa of original T91 in air at 550 °C. No signs of LBE influence are detected. The surface modified specimens tested at high stress levels instead had creep-rupture times similar to T91 (original state) tested in air. The thin oxide layers formed on the surface modified steel samples are less susceptible to crack formation and therefore to lead-alloy enhanced creep.

  2. Structures of FolT in substrate-bound and substrate-released conformations reveal a gating mechanism for ECF transporters

    NASA Astrophysics Data System (ADS)

    Zhao, Qin; Wang, Chengcheng; Wang, Chengyuan; Guo, Hui; Bao, Zhihao; Zhang, Minhua; Zhang, Peng

    2015-07-01

    Energy-coupling factor (ECF) transporters are a new family of ABC transporters that consist of four subunits, two cytoplasmic ATPases EcfA and EcfA' and two transmembrane proteins namely EcfS for substrate-specific binding and EcfT for energy coupling. Here, we report the 3.2-Å resolution crystal structure of the EcfS protein of a folate ECF transporter from Enterococcus faecalis-EfFolT, a close homologue of FolT from Lactobacillus brevis-LbFolT. Structural and biochemical analyses reveal the residues constituting the folate-binding pocket and determining the substrate-binding specificity. Structural comparison of the folate-bound EfFolT with the folate-free LbFolT contained in the holotransporter complex discloses significant conformational change at the L1 loop, and reveals a gating mechanism of ECF transporters in which the L1 loop of EcfS acts as a gate in the substrate binding and release.

  3. The Toxicity Estimation Software Tool (T.E.S.T.)

    EPA Science Inventory

    The Toxicity Estimation Software Tool (T.E.S.T.) has been developed to estimate toxicological values for aquatic and mammalian species considering acute and chronic endpoints for screening purposes within TSCA and REACH programs.

  4. Effects of a common transcranial direct current stimulation (tDCS) protocol on motor evoked potentials found to be highly variable within individuals over 9 testing sessions.

    PubMed

    Horvath, Jared Cooney; Vogrin, Simon J; Carter, Olivia; Cook, Mark J; Forte, Jason D

    2016-09-01

    Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode; 3 cathode; 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the individual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test-retest reliability [anode: ICC(2,1) = 0.062; cathode: ICC(2,1) = 0.055] and moderate sham test-retest reliability [ICC(2,1) = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level. In addition, no significant effects of tDCS on MEP amplitude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations.

  5. Elevated high-sensitive troponin T in negative stress test individuals.

    PubMed

    Brzezinski, Rafael Y; Fisher, Eyal; Ehrenwald, Michal; Shefer, Gabi; Stern, Naftali; Shapira, Itzhak; Zeltser, David; Berliner, Shlomo; Shenhar-Tsarfaty, Shani; Milwidsky, Assi; Rogowski, Ori

    2018-06-01

    The exercise ECG stress test (EST) is still the first step of work-up in intermediate risk patients in many clinical scenarios. High-sensitive cardiac troponin T (hs-cTnT) elevation is related to future cardiovascular events in the general population and in patients with ischaemic heart disease. The relation between these 2 tests is not well described. A total of 2780 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 49 years, 79% men) were analysed. Multiple physiologic and metabolic parameters including hs-cTnT were collected. All participants completed an EST manually reviewed by a cardiologist. A positive EST was documented in 224 subjects (8%). The majority (91%) of participants with hs-cTnT levels of 5-14 ng/L had a negative EST as well as 89.3% of subjects with levels >14 ng/L. The proportion of subjects with a positive EST and detectable hs-cTnT levels (>5 ng/L) was not significantly greater compared to those with a negative EST (53.1% vs 46.2%, respectively, P = .09). Among subjects referred for EST as part of an annual health survey, we found no significant association between EST results to hs-cTnT detection. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

  6. Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

    NASA Technical Reports Server (NTRS)

    Armoundas, A. A.; Rosenbaum, D. S.; Ruskin, J. N.; Garan, H.; Cohen, R. J.

    1998-01-01

    OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular

  7. 40 CFR Appendix IV to Part 265 - Tests for Significance

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... introductory statistics texts. ... student's t-test involves calculation of the value of a t-statistic for each comparison of the mean... parameter with its initial background concentration or value. The calculated value of the t-statistic must...

  8. Prognostic significance of electrophysiological tests for facial nerve outcome in vestibular schwannoma surgery.

    PubMed

    van Dinther, J J S; Van Rompaey, V; Somers, T; Zarowski, A; Offeciers, F E

    2011-01-01

    To assess the prognostic significance of pre-operative electrophysiological tests for facial nerve outcome in vestibular schwannoma surgery. Retrospective study design in a tertiary referral neurology unit. We studied a total of 123 patients with unilateral vestibular schwannoma who underwent microsurgical removal of the lesion. Nine patients were excluded because they had clinically abnormal pre-operative facial function. Pre-operative electrophysiological facial nerve function testing (EPhT) was performed. Short-term (1 month) and long-term (1 year) post-operative clinical facial nerve function were assessed. When pre-operative facial nerve function, evaluated by EPhT, was normal, the outcome from clinical follow-up at 1-month post-operatively was excellent in 78% (i.e. HB I-II) of patients, moderate in 11% (i.e. HB III-IV), and bad in 11% (i.e. HB V-VI). After 1 year, 86% had excellent outcomes, 13% had moderate outcomes, and 1% had bad outcomes. Of all patients with normal clinical facial nerve function, 22% had an abnormal EPhT result and 78% had a normal result. No statistically significant differences could be observed in short-term and long-term post-operative facial function between the groups. In this study, electrophysiological tests were not able to predict facial nerve outcome after vestibular schwannoma surgery. Tumour size remains the best pre-operative prognostic indicator of facial nerve function outcome, i.e. a better outcome in smaller lesions.

  9. Whole-lesion apparent diffusion coefficient histogram analysis: significance in T and N staging of gastric cancers.

    PubMed

    Liu, Song; Zhang, Yujuan; Chen, Ling; Guan, Wenxian; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang

    2017-10-02

    Whole-lesion apparent diffusion coefficient (ADC) histogram analysis has been introduced and proved effective in assessment of multiple tumors. However, the application of whole-volume ADC histogram analysis in gastrointestinal tumors has just started and never been reported in T and N staging of gastric cancers. Eighty patients with pathologically confirmed gastric carcinomas underwent diffusion weighted (DW) magnetic resonance imaging before surgery prospectively. Whole-lesion ADC histogram analysis was performed by two radiologists independently. The differences of ADC histogram parameters among different T and N stages were compared with independent-samples Kruskal-Wallis test. Receiver operating characteristic (ROC) analysis was performed to evaluate the performance of ADC histogram parameters in differentiating particular T or N stages of gastric cancers. There were significant differences of all the ADC histogram parameters for gastric cancers at different T (except ADC min and ADC max ) and N (except ADC max ) stages. Most ADC histogram parameters differed significantly between T1 vs T3, T1 vs T4, T2 vs T4, N0 vs N1, N0 vs N3, and some parameters (ADC 5% , ADC 10% , ADC min ) differed significantly between N0 vs N2, N2 vs N3 (all P < 0.05). Most parameters except ADC max performed well in differentiating different T and N stages of gastric cancers. Especially for identifying patients with and without lymph node metastasis, the ADC 10% yielded the largest area under the ROC curve of 0.794 (95% confidence interval, 0.677-0.911). All the parameters except ADC max showed excellent inter-observer agreement with intra-class correlation coefficients higher than 0.800. Whole-volume ADC histogram parameters held great potential in differentiating different T and N stages of gastric cancers preoperatively.

  10. Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock.

    PubMed

    Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Poterucha, Joseph T; Kashyap, Rahul; Kashani, Kianoush; Jaffe, Allan S; Jentzer, Jacob C

    2017-09-09

    Troponin-T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin-T testing in the prognostication of these patients. This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin-T and significant delta troponin-T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and lengths of stay. During this 8-year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin-T ≥0.01 ng/mL. Serial troponin-T values were available in 732 (78%) patients. Elevated admission troponin-T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin-T was associated with higher severity of illness. Admission log 10 troponin-T was associated with unadjusted in-hospital (odds ratio 1.6; P =0.003) and 1-year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin-T and log 10 delta troponin-T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin-T remained an independent predictor of in-hospital mortality (odds ratio 1.4; P =0.04) and 1-year survival (hazard ratio 1.3; P =0.008). In patients with sepsis and septic shock, elevated admission troponin-T was associated with higher short- and long-term mortality. Routine serial troponin-T testing did not add incremental prognostic value in these patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  11. Determining Differences in Efficacy of Two Disinfectants Using t-Tests.

    ERIC Educational Resources Information Center

    Brehm, Michael A.; And Others

    1996-01-01

    Presents an experiment to compare the effectiveness of 95% ethanol to 20% bleach as disinfectants using t-tests for the statistical analysis of the data. Reports that bleach is a better disinfectant. Discusses the statistical and practical significance of the results. (JRH)

  12. Differentiation of Trypanosoma brucei, T. rhodesiense, and T. gambiense by the indirect fluorescent antibody test

    PubMed Central

    Latif, B. M. A.; Adam, Katherine M. G.

    1973-01-01

    Epidemiological studies, if they are to lead to appropriate preventive procedures, require knowledge of the host distribution of the parasite. Progress in the epidemiology of African trypanosomiasis is restricted by the lack of a reliable and simple method of differentiating Trypanosoma brucei, T. rhodesiense, and T. gambiense. The recently introduced blood inoculation infectivity test promises to fulfil this need by distinguishing T. brucei from T. rhodesiense, but it would not be suitable for separating T. brucei from T. gambiense, since rats and mice are frequently refractory to infection by fresh isolates of T. gambiense. Previous studies had indicated that the indirect fluorescent antibody test might differentiate not only the subgenera of the salivarian trypanosome species but also members of the subgenus Trypanozoon. A method of performing the test is described that enables T. brucei, T. rhodesiense, and T. gambiense to be differentiated by the titre of the sera. The method might be used in conjunction with the blood inoculation infectivity test to distinguish between new isolates of the subgenus Trypanozoon in East Africa, and also to search for possible animal reservoirs of T. gambiense in West Africa. PMID:4587481

  13. The Interrupted Time Series as Quasi-Experiment: Three Tests of Significance. A Fortran Program for the CDC 3400 Computer.

    ERIC Educational Resources Information Center

    Sween, Joyce; Campbell, Donald T.

    Computational formulae for the following three tests of significance, useful in the interrupted time series design, are given: (1) a "t" test (Mood, 1950) for the significance of the first post-change observation from a value predicted by a linear fit of the pre-change observations; (2) an "F" test (Walker and Lev, 1953) of the…

  14. Validation of a modification to Performance-Tested Method 070601: Reveal Listeria Test for detection of Listeria spp. in selected foods and selected environmental samples.

    PubMed

    Alles, Susan; Peng, Linda X; Mozola, Mark A

    2009-01-01

    A modification to Performance-Tested Method (PTM) 070601, Reveal Listeria Test (Reveal), is described. The modified method uses a new media formulation, LESS enrichment broth, in single-step enrichment protocols for both foods and environmental sponge and swab samples. Food samples are enriched for 27-30 h at 30 degrees C and environmental samples for 24-48 h at 30 degrees C. Implementation of these abbreviated enrichment procedures allows test results to be obtained on a next-day basis. In testing of 14 food types in internal comparative studies with inoculated samples, there was a statistically significant difference in performance between the Reveal and reference culture [U.S. Food and Drug Administration's Bacteriological Analytical Manual (FDA/BAM) or U.S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS)] methods for only a single food in one trial (pasteurized crab meat) at the 27 h enrichment time point, with more positive results obtained with the FDA/BAM reference method. No foods showed statistically significant differences in method performance at the 30 h time point. Independent laboratory testing of 3 foods again produced a statistically significant difference in results for crab meat at the 27 h time point; otherwise results of the Reveal and reference methods were statistically equivalent. Overall, considering both internal and independent laboratory trials, sensitivity of the Reveal method relative to the reference culture procedures in testing of foods was 85.9% at 27 h and 97.1% at 30 h. Results from 5 environmental surfaces inoculated with various strains of Listeria spp. showed that the Reveal method was more productive than the reference USDA-FSIS culture procedure for 3 surfaces (stainless steel, plastic, and cast iron), whereas results were statistically equivalent to the reference method for the other 2 surfaces (ceramic tile and sealed concrete). An independent laboratory trial with ceramic tile inoculated with L

  15. Test wells T23, T29, and T30, White Sands Missile Range and Fort Bliss Military Reservation, Dona Ana County, New Mexico

    USGS Publications Warehouse

    Myers, R.G.; Pinckley, K.M.

    1984-01-01

    Three test wells, T23, T29, and T30, were drilled in south-central New Mexico as part of a joint military training program sponsored by the U.S. Army in November 1982. Test well T23 was drilled as an exploratory and monitoring well in the proposed Soledad well field at the Fort Bliss Military Reservation. Test wells T29 and T30 were drilled at White Sands Missile Range. Test well T29 was drilled as an observation well in the vicinity of the outfall channel from the sewage treatment plant. Test well T30 was drilled as an observation well for a landfill south of the well site. Information obtained from these wells includes lithologic logs for all wells and borehole-geophysical logs from the cased wells for test wells T29 and T30. (USGS)

  16. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    NASA Astrophysics Data System (ADS)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  17. Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma.

    PubMed Central

    Starzynska, T.; Marsh, P. J.; Schofield, P. F.; Roberts, S. A.; Myers, K. A.; Stern, P. L.

    1994-01-01

    The 5T4 oncofetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. The 5T4 antigen phenotype of 72 colorectal cancers has been compared with the clinical outcome of the patients in order to assess its relationship with prognosis. Forty per cent of tumours were 5T4 positive; the remainder were either unlabelled or exhibited stroma-associated labelling only. There was a significant correlation between 5T4 expression in the malignant cells and unfavourable course of disease (P < 0.001). The 5 year survival with 5T4-positive tumours was 22% compared with 75% for patients with 5T4-negative tumours; median survival was 24 versus > 90 months respectively. Stratified analysis showed that 5T4 antigen tumour positivity was acting independently of each of stage, site of tumour, age or sex. There were significant differences in survival for patients with Dukes' B and C stage carcinomas (P = 0.001 and P = 0.034). The results suggest that in colorectal cancer immunohistochemical assessment of 5T4 expression may be useful in identifying patients at high risk for tumour recurrence and for whom additional treatment strategies might be most appropriate. Images Figure 1 PMID:8180020

  18. Tuberculin skin testing and T-SPOT.TB in internationally adopted children.

    PubMed

    Spicer, Kevin B; Turner, Joanne; Wang, Shu-Hua; Koranyi, Katalin; Powell, Dwight A

    2015-06-01

    Diagnosis of latent tuberculosis infection is a problem in children because of lack of a diagnostic standard and potential impact of previous Bacille Calmette-Guérin vaccination and exposure to environmental mycobacteria. Effectiveness and usefulness of interferon-gamma release assays in infants and younger children have yet to be clearly demonstrated. Prospective cohort study including 109 children (4 months to 16 years) seen in an international adoption clinic at Nationwide Children's Hospital, Columbus, OH. Children were adopted from 14 countries, mostly (72.5%) from China, Russia and Ethiopia. Correspondence between tuberculin skin test (TST) and the T-SPOT.TB assay was evaluated. Factors associated with positive results on the TST and T-SPOT.TB were determined, and the impact of age on test performance was specifically addressed. TST was positive in 23.4% (25 of 107). T-SPOT.TB was positive in 4.6% (5 of 109). Overall agreement between TST and T-SPOT.TB was 71%, with prevalence-adjusted, bias-adjusted Kappa of 0.68. History of Mycobacterium tuberculosis exposure was associated with positive results on TST (odds ratio: 25.4, 95% confidence interval: 4.8-261.6, exact logistic regression) and T-SPOT.TB (odds ratio: 78.9, 95% confidence interval: 9.7-∞). All 5 children with positive T-SPOT.TB had TST induration ≥15 mm. No patient less than 1 year of age (n = 17) had positive TST or T-SPOT.TB. Positive TST was not associated with Bacille Calmette-Guérin vaccination or scar. TST was positive in a significant percentage of international adoptees. T-SPOT.TB was rarely positive and discordant results reflected negative T-SPOT.TB with positive TST. In this population latent tuberculosis infection may be over-estimated by TST. Regardless, in our context at the time of the study, treatment decisions were based upon TST results, not results of the T-SPOT.TB assay. Age was consistently associated with findings on TST and T-SPOT.TB with no positive result on either

  19. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination.

    PubMed

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R

    2012-06-29

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.

  20. Wide-scale quantitative phosphoproteomic analysis reveals that cold treatment of T cells closely mimics soluble antibody stimulation

    PubMed Central

    Ji, Qinqin; Salomon, Arthur R.

    2015-01-01

    The activation of T-lymphocytes through antigen-mediated T-cell receptor (TCR) clustering is vital in regulating the adaptive-immune response. Although T cell receptor signaling has been extensively studied, the fundamental mechanisms for signal initiation are not fully understood. Reduced temperature initiated some of the hallmarks of TCR signaling such as increased phosphorylation and activation on ERK and calcium release from the endoplasmic reticulum as well as coalesce T-cell membrane microdomains. The precise mechanism of TCR signaling initiation due to temperature change remains obscure. One critical question is whether signaling initiated by cold treatment of T cells differs from signaling initiated by crosslinking of the T cell receptor. To address this uncertainty, a wide-scale, quantitative mass spectrometry-based phosphoproteomic analysis was performed on T cells stimulated either by temperature shift or through crosslinking of the TCR. Careful statistical comparison between the two stimulations revealed a striking level of identity between the subset of 339 sites that changed significantly with both stimulations. This study demonstrates for the first time, at unprecedented detail, that T cell cold treatment was sufficient to initiate signaling patterns nearly identical to soluble antibody stimulation, shedding new light on the mechanism of activation of these critically important immune cells. PMID:25839225

  1. Phosphoproteomics Reveals Regulatory T Cell-Mediated DEF6 Dephosphorylation That Affects Cytokine Expression in Human Conventional T Cells

    PubMed Central

    Joshi, Rubin N.; Binai, Nadine A.; Marabita, Francesco; Sui, Zhenhua; Altman, Amnon; Heck, Albert J. R.; Tegnér, Jesper; Schmidt, Angelika

    2017-01-01

    Regulatory T cells (Tregs) control key events of immune tolerance, primarily by suppression of effector T cells. We previously revealed that Tregs rapidly suppress T cell receptor (TCR)-induced calcium store depletion in conventional CD4+CD25− T cells (Tcons) independently of IP3 levels, consequently inhibiting NFAT signaling and effector cytokine expression. Here, we study Treg suppression mechanisms through unbiased phosphoproteomics of primary human Tcons upon TCR stimulation and Treg-mediated suppression, respectively. Tregs induced a state of overall decreased phosphorylation as opposed to TCR stimulation. We discovered novel phosphosites (T595_S597) in the DEF6 (SLAT) protein that were phosphorylated upon TCR stimulation and conversely dephosphorylated upon coculture with Tregs. Mutation of these DEF6 phosphosites abrogated interaction of DEF6 with the IP3 receptor and affected NFAT activation and cytokine transcription in primary Tcons. This novel mechanism and phosphoproteomics data resource may aid in modifying sensitivity of Tcons to Treg-mediated suppression in autoimmune disease or cancer. PMID:28993769

  2. The t-test: An Influential Inferential Tool in Chaplaincy and Other Healthcare Research.

    PubMed

    Jankowski, Katherine R B; Flannelly, Kevin J; Flannelly, Laura T

    2018-01-01

    The t-test developed by William S. Gosset (also known as Student's t-test and the two-sample t-test) is commonly used to compare one sample mean on a measure with another sample mean on the same measure. The outcome of the t-test is used to draw inferences about how different the samples are from each other. It is probably one of the most frequently relied upon statistics in inferential research. It is easy to use: a researcher can calculate the statistic with three simple tools: paper, pen, and a calculator. A computer program can quickly calculate the t-test for large samples. The ease of use can result in the misuse of the t-test. This article discusses the development of the original t-test, basic principles of the t-test, two additional types of t-tests (the one-sample t-test and the paired t-test), and recommendations about what to consider when using the t-test to draw inferences in research.

  3. [The expression and significance of RORγT in periapical granulomas and radicular cysts].

    PubMed

    Lang, Xiao-ying; Li, Song

    2014-08-01

    To identify retinoic acid-related orphan nuclear receptor-γT (RORγT), the specific markers of T helper 17 (Th17) cells by immunohistochemical analysis to confirm the presence of Th17 cells in periapical lesions. Eighteen radicular cysts (RCs) and 22 periapical granulomas (PGs) were collected in the Department of Oral Pathology after periapical surgery as the experimental samples. Five alveolar bone samples were obtained from a group of impacted third molars recommended for extraction as the control samples. The protein expression of RORγT was measured by immunohistochemical analysis for all samples. In addition, the protein expression of IL-17 was measured at the same time. Statistical analysis was performed using SPSS 17.0 software package to evaluate the differences of expression of RORγT and IL-17 according to type of lesion (PG vs. RC vs. control group) and intensity of the inflammatory infiltration (mild vs. moderate vs. severe vs. control group). RORγT+ cells were detected in all periapical lesions tissues, and the expression of RORγT was significantly higher in periapical lesions than in normal tissues which had no expression of RORγT (P<0.05). Significant differences in the expression of RORγT were observed among healthy tissues, lesions with mild inflammation, moderate inflammation and severe inflammation (P<0.05), respectively. Positive correlations between RORγT and IL-17 protein levels were observed in PGs (r=0.935,P<0.05) and RCs (r=0.803,P<0.05), respectively. The results demonstrates a significant increase in the expression of RORγT in patients suffering from periapical lesions in comparison with normal control subjects, indicating that Th17 cells are more likely to exist in periapical lesions.

  4. Significance testing as perverse probabilistic reasoning

    PubMed Central

    2011-01-01

    Truth claims in the medical literature rely heavily on statistical significance testing. Unfortunately, most physicians misunderstand the underlying probabilistic logic of significance tests and consequently often misinterpret their results. This near-universal misunderstanding is highlighted by means of a simple quiz which we administered to 246 physicians at two major academic hospitals, on which the proportion of incorrect responses exceeded 90%. A solid understanding of the fundamental concepts of probability theory is becoming essential to the rational interpretation of medical information. This essay provides a technically sound review of these concepts that is accessible to a medical audience. We also briefly review the debate in the cognitive sciences regarding physicians' aptitude for probabilistic inference. PMID:21356064

  5. North-South S and T gap

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moghadam, A.A.

    1985-01-01

    The objectives of this study were (1) to demonstrate the existence of the science and technology (S and T) gap between developed countries (DCs) or the north, and less developed countries (LDCs) or the south; (2) to test the hypothesis that there exists a critical mass with respect to population, gross domestic product (GDP), per capita income, and literacy rate below which S and T development is insignificant; and (3) to recommend possible remedial actions for reducing this gap. The research comprises a thorough review of the existing literature, and an extensive analysis of 1976-78 and 1980-82 statistics for 66more » countries, presenting a global picture of the S and T gap in the free world. A comprehensive account was given of the S and T status for Britain, Germany, United States, Japan, Brazil, Mexico, South Korea, Hong Kong, Singapore, Taiwan, Egypt, and Nigeria. A plot of S and T indicators versus independent variables for the 66 counties clearly indicated the existence of the North-South S and T gap. The test of the critical hypothesis, using t distribution, revealed that population size does not have a significant impact on the development or deployment of S and T. This test with respect to GDP indicated that greater GDPs would facilitate the progress of S and T. The results for per capita income were similar. Adequate infrastructure had the greatest impact on absorption, deployment, and maintenance of S and T for development. It was also indicated that with literacy rates below 40% no significant S and T activity can be expected.« less

  6. The PHA Test Reflects Acquired T-Cell Mediated Immunocompetence in Birds

    PubMed Central

    Tella, José L.; Lemus, Jesús A.; Carrete, Martina; Blanco, Guillermo

    2008-01-01

    Background cological immunology requires techniques to reliably measure immunocompetence in wild vertebrates. The PHA-skin test, involving subcutaneous injection of a mitogen (phytohemagglutinin, PHA) and measurement of subsequent swelling as a surrogate of T-cell mediated immunocompetence, has been the test of choice due to its practicality and ease of use in the field. However, mechanisms involved in local immunological and inflammatory processes provoked by PHA are poorly known, and its use and interpretation as an acquired immune response is currently debated. Methodology Here, we present experimental work using a variety of parrot species, to ascertain whether PHA exposure produces larger secondary than primary responses as expected if the test reflects acquired immunocompetence. Moreover, we simultaneously quantified T-lymphocyte subsets (CD4+, CD5+ and CD8+) and plasma proteins circulating in the bloodstream, potentially involved in the immunological and inflammatory processes, through flow cytometry and electrophoresis. Principal Findings Our results showed stronger responses after a second PHA injection, independent of species, time elapsed and changes in body mass of birds between first and second injections, thus supporting the adaptive nature of this immune response. Furthermore, the concomitant changes in the plasma concentrations of T-lymphocyte subsets and globulins indicate a causal link between the activation of the T-cell mediated immune system and local tissue swelling. Conclusions/Significance These findings justify the widespread use of the PHA-skin test as a reliable evaluator of acquired T-cell mediated immunocompetence in diverse biological disciplines. Further experimental research should be aimed at evaluating the relative role of innate immunocompetence in wild conditions, where the access to dietary proteins varies more than in captivity, and to ascertain how PHA responses relate to particular host-parasite interactions. PMID:18820730

  7. Test wells T21, T22, and T25, White Sands Missile Range, Dona Ana County, New Mexico

    USGS Publications Warehouse

    Myers, R.G.

    1983-01-01

    Three test wells, T21, T22, and T25, were drilled at White Sands Missile Range in south-central New Mexico as part of a joint military program sponsored by the U.S. Army in September 1982. T21 and T22 were drilled as observation wells for two old landfills. T25 was drilled as an exploratory hole to obtain lithologic and borehole-geophysical data in the vicinity of the proposed replacement well for Supply Well 15. Information obtained from these wells includes borehole-geophysical and driller's logs.

  8. Multivariate Welch t-test on distances

    PubMed Central

    2016-01-01

    Motivation: Permutational non-Euclidean analysis of variance, PERMANOVA, is routinely used in exploratory analysis of multivariate datasets to draw conclusions about the significance of patterns visualized through dimension reduction. This method recognizes that pairwise distance matrix between observations is sufficient to compute within and between group sums of squares necessary to form the (pseudo) F statistic. Moreover, not only Euclidean, but arbitrary distances can be used. This method, however, suffers from loss of power and type I error inflation in the presence of heteroscedasticity and sample size imbalances. Results: We develop a solution in the form of a distance-based Welch t-test, TW2, for two sample potentially unbalanced and heteroscedastic data. We demonstrate empirically the desirable type I error and power characteristics of the new test. We compare the performance of PERMANOVA and TW2 in reanalysis of two existing microbiome datasets, where the methodology has originated. Availability and Implementation: The source code for methods and analysis of this article is available at https://github.com/alekseyenko/Tw2. Further guidance on application of these methods can be obtained from the author. Contact: alekseye@musc.edu PMID:27515741

  9. Multivariate Welch t-test on distances.

    PubMed

    Alekseyenko, Alexander V

    2016-12-01

    Permutational non-Euclidean analysis of variance, PERMANOVA, is routinely used in exploratory analysis of multivariate datasets to draw conclusions about the significance of patterns visualized through dimension reduction. This method recognizes that pairwise distance matrix between observations is sufficient to compute within and between group sums of squares necessary to form the (pseudo) F statistic. Moreover, not only Euclidean, but arbitrary distances can be used. This method, however, suffers from loss of power and type I error inflation in the presence of heteroscedasticity and sample size imbalances. We develop a solution in the form of a distance-based Welch t-test, [Formula: see text], for two sample potentially unbalanced and heteroscedastic data. We demonstrate empirically the desirable type I error and power characteristics of the new test. We compare the performance of PERMANOVA and [Formula: see text] in reanalysis of two existing microbiome datasets, where the methodology has originated. The source code for methods and analysis of this article is available at https://github.com/alekseyenko/Tw2 Further guidance on application of these methods can be obtained from the author. alekseye@musc.edu. © The Author 2016. Published by Oxford University Press.

  10. A shift from significance test to hypothesis test through power analysis in medical research.

    PubMed

    Singh, G

    2006-01-01

    Medical research literature until recently, exhibited substantial dominance of the Fisher's significance test approach of statistical inference concentrating more on probability of type I error over Neyman-Pearson's hypothesis test considering both probability of type I and II error. Fisher's approach dichotomises results into significant or not significant results with a P value. The Neyman-Pearson's approach talks of acceptance or rejection of null hypothesis. Based on the same theory these two approaches deal with same objective and conclude in their own way. The advancement in computing techniques and availability of statistical software have resulted in increasing application of power calculations in medical research and thereby reporting the result of significance tests in the light of power of the test also. Significance test approach, when it incorporates power analysis contains the essence of hypothesis test approach. It may be safely argued that rising application of power analysis in medical research may have initiated a shift from Fisher's significance test to Neyman-Pearson's hypothesis test procedure.

  11. Rehearsal significantly improves immediate and delayed recall on the Rey Auditory Verbal Learning Test.

    PubMed

    Hessen, Erik

    2011-10-01

    A repeated observation during memory assessment with the Rey Auditory Verbal Learning Test (RAVLT) is that patients who spontaneously employ a memory rehearsal strategy by repeating the word list more than once achieve better scores than patients who only repeat the word list once. This observation led to concern about the ability of the standard test procedure of RAVLT and similar tests in eliciting the best possible recall scores. The purpose of the present study was to test the hypothesis that a rehearsal recall strategy of repeating the word list more than once would result in improved scores of recall on the RAVLT. We report on differences in outcome after standard administration and after experimental administration on Immediate and Delayed Recall measures from the RAVLT of 50 patients. The experimental administration resulted in significantly improved scores for all the variables employed. Additionally, it was found that patients who failed effort screening showed significantly poorer improvement on Delayed Recall compared with those who passed the effort screening. The general clear improvement both in raw scores and T-scores demonstrates that recall performance can be significantly influenced by the strategy of the patient or by small variations in instructions by the examiner.

  12. Test wells T27 and T28, White Sands Missile Range, Dona Ana County, New Mexico

    USGS Publications Warehouse

    Myers, R.G.; Pinckley, K.M.

    1985-01-01

    Two test wells, T27 and T28, were drilled at White Sands Missile Range in south-central New Mexico as part of a joint military training program sponsored by the U.S. Army in February and March 1983. Test wells T27 and T28 were drilled as observation wells in the vicinity of the Liquid Propellant Storage Area. Information obtained from these wells includes lithologic logs, driller 's logs, and borehole-geophysical logs from the cased wells. (USGS)

  13. Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen.

    PubMed

    Lambert Emo, Kris; Hyun, Young-Min; Reilly, Emma; Barilla, Christopher; Gerber, Scott; Fowell, Deborah; Kim, Minsoo; Topham, David J

    2016-09-01

    During a primary influenza infection, cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells. The factors that regulate T cell motility in the infected airway tissue are not well known. To more precisely study T cell infiltration of the airways, we developed an experimental model system using the trachea as a site where live imaging can be performed. CD8+ T cell motility was dynamic with marked changes in motility on different days of the infection. In particular, significant changes in average cell velocity and confinement were evident on days 8-10 during which the T cells abruptly but transiently increase velocity on day 9. Experiments to distinguish whether infection itself or antigen affect motility revealed that it is antigen, not active infection per se that likely affects these changes as blockade of peptide/MHC resulted in increased velocity. These observations demonstrate that influenza tracheitis provides a robust experimental foundation to study molecular regulation of T cell motility during acute virus infection.

  14. Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen

    PubMed Central

    Lambert Emo, Kris; Hyun, Young-min; Barilla, Christopher; Gerber, Scott; Fowell, Deborah; Kim, Minsoo

    2016-01-01

    During a primary influenza infection, cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells. The factors that regulate T cell motility in the infected airway tissue are not well known. To more precisely study T cell infiltration of the airways, we developed an experimental model system using the trachea as a site where live imaging can be performed. CD8+ T cell motility was dynamic with marked changes in motility on different days of the infection. In particular, significant changes in average cell velocity and confinement were evident on days 8–10 during which the T cells abruptly but transiently increase velocity on day 9. Experiments to distinguish whether infection itself or antigen affect motility revealed that it is antigen, not active infection per se that likely affects these changes as blockade of peptide/MHC resulted in increased velocity. These observations demonstrate that influenza tracheitis provides a robust experimental foundation to study molecular regulation of T cell motility during acute virus infection. PMID:27644089

  15. Significance levels for studies with correlated test statistics.

    PubMed

    Shi, Jianxin; Levinson, Douglas F; Whittemore, Alice S

    2008-07-01

    When testing large numbers of null hypotheses, one needs to assess the evidence against the global null hypothesis that none of the hypotheses is false. Such evidence typically is based on the test statistic of the largest magnitude, whose statistical significance is evaluated by permuting the sample units to simulate its null distribution. Efron (2007) has noted that correlation among the test statistics can induce substantial interstudy variation in the shapes of their histograms, which may cause misleading tail counts. Here, we show that permutation-based estimates of the overall significance level also can be misleading when the test statistics are correlated. We propose that such estimates be conditioned on a simple measure of the spread of the observed histogram, and we provide a method for obtaining conditional significance levels. We justify this conditioning using the conditionality principle described by Cox and Hinkley (1974). Application of the method to gene expression data illustrates the circumstances when conditional significance levels are needed.

  16. HEALTH SIGNIFICANCE OF PULMONARY FUNCTION TESTS

    EPA Science Inventory

    As the sensitivity and precision of functional tests improves, we become increasingly able to measure responses to pollutant exposures with little, if any, demonstrable health significance. Proper interpretation of such functional responses generally requires an ability to evalua...

  17. Calculating p-values and their significances with the Energy Test for large datasets

    NASA Astrophysics Data System (ADS)

    Barter, W.; Burr, C.; Parkes, C.

    2018-04-01

    The energy test method is a multi-dimensional test of whether two samples are consistent with arising from the same underlying population, through the calculation of a single test statistic (called the T-value). The method has recently been used in particle physics to search for samples that differ due to CP violation. The generalised extreme value function has previously been used to describe the distribution of T-values under the null hypothesis that the two samples are drawn from the same underlying population. We show that, in a simple test case, the distribution is not sufficiently well described by the generalised extreme value function. We present a new method, where the distribution of T-values under the null hypothesis when comparing two large samples can be found by scaling the distribution found when comparing small samples drawn from the same population. This method can then be used to quickly calculate the p-values associated with the results of the test.

  18. A SIGNIFICANCE TEST FOR THE LASSO1

    PubMed Central

    Lockhart, Richard; Taylor, Jonathan; Tibshirani, Ryan J.; Tibshirani, Robert

    2014-01-01

    In the sparse linear regression setting, we consider testing the significance of the predictor variable that enters the current lasso model, in the sequence of models visited along the lasso solution path. We propose a simple test statistic based on lasso fitted values, called the covariance test statistic, and show that when the true model is linear, this statistic has an Exp(1) asymptotic distribution under the null hypothesis (the null being that all truly active variables are contained in the current lasso model). Our proof of this result for the special case of the first predictor to enter the model (i.e., testing for a single significant predictor variable against the global null) requires only weak assumptions on the predictor matrix X. On the other hand, our proof for a general step in the lasso path places further technical assumptions on X and the generative model, but still allows for the important high-dimensional case p > n, and does not necessarily require that the current lasso model achieves perfect recovery of the truly active variables. Of course, for testing the significance of an additional variable between two nested linear models, one typically uses the chi-squared test, comparing the drop in residual sum of squares (RSS) to a χ12 distribution. But when this additional variable is not fixed, and has been chosen adaptively or greedily, this test is no longer appropriate: adaptivity makes the drop in RSS stochastically much larger than χ12 under the null hypothesis. Our analysis explicitly accounts for adaptivity, as it must, since the lasso builds an adaptive sequence of linear models as the tuning parameter λ decreases. In this analysis, shrinkage plays a key role: though additional variables are chosen adaptively, the coefficients of lasso active variables are shrunken due to the l1 penalty. Therefore, the test statistic (which is based on lasso fitted values) is in a sense balanced by these two opposing properties—adaptivity and

  19. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory

    PubMed Central

    Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi

    2018-01-01

    Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

  20. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

    PubMed

    Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi; Tanaka, Teruyuki

    2018-01-01

    Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

  1. Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study

    PubMed Central

    Hozumi, Hironao; Enomoto, Noriyuki; Kono, Masato; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Sumikawa, Hiromitsu; Johkoh, Takeshi; Nakashima, Ran; Imura, Yoshitaka; Mimori, Tsuneyo; Suda, Takafumi

    2015-01-01

    Background In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established. Objective We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients. Methods Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group). Results Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01). Conclusions The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD. PMID:25789468

  2. Automated Formal Testing of C API Using T2C Framework

    NASA Astrophysics Data System (ADS)

    Khoroshilov, Alexey V.; Rubanov, Vladimir V.; Shatokhin, Eugene A.

    A problem of automated test development for checking basic functionality of program interfaces (API) is discussed. Different technologies and corresponding tools are surveyed. And T2C technology developed in ISPRAS is presented. The technology and associated tools facilitate development of "medium quality" (and "medium cost") tests. An important feature of T2C technology is that it enforces that each check in a developed test is explicitly linked to the corresponding place in the standard. T2C tools provide convenient means to create such linkage. The results of using T2C are considered by example of a project for testing interfaces of Linux system libraries defined by the LSB standard.

  3. T-cell involvement in drug-induced acute generalized exanthematous pustulosis

    PubMed Central

    Britschgi, Markus; Steiner, Urs C.; Schmid, Simone; Depta, Jan P.H.; Senti, Gabriela; Bircher, Andreas; Burkhart, Christoph; Yawalkar, Nikhil; Pichler, Werner J.

    2001-01-01

    Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate consisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotypic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell receptor Vβ-expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced significantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction. PMID:11390425

  4. Tests of Statistical Significance Made Sound

    ERIC Educational Resources Information Center

    Haig, Brian D.

    2017-01-01

    This article considers the nature and place of tests of statistical significance (ToSS) in science, with particular reference to psychology. Despite the enormous amount of attention given to this topic, psychology's understanding of ToSS remains deficient. The major problem stems from a widespread and uncritical acceptance of null hypothesis…

  5. Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing and phylogeny

    PubMed Central

    Messmer, Marie; Pütz, Joern; Suzuki, Takeo; Suzuki, Tsutomu; Sauter, Claude; Sissler, Marie; Catherine, Florentz

    2009-01-01

    Primary and secondary structures of mammalian mitochondrial (mt) tRNAs are divergent from canonical tRNA structures due to highly skewed nucleotide content and large size variability of D- and T-loops. The nonconservation of nucleotides involved in the expected network of tertiary interactions calls into question the rules governing a functional L-shaped three-dimensional (3D) structure. Here, we report the solution structure of human mt-tRNAAsp in its native post-transcriptionally modified form and as an in vitro transcript. Probing performed with nuclease S1, ribonuclease V1, dimethylsulfate, diethylpyrocarbonate and lead, revealed several secondary structures for the in vitro transcribed mt-tRNAAsp including predominantly the cloverleaf. On the contrary, the native tRNAAsp folds into a single cloverleaf structure, highlighting the contribution of the four newly identified post-transcriptional modifications to correct folding. Reactivities of nucleotides and phosphodiester bonds in the native tRNA favor existence of a full set of six classical tertiary interactions between the D-domain and the variable region, forming the core of the 3D structure. Reactivities of D- and T-loop nucleotides support an absence of interactions between these domains. According to multiple sequence alignments and search for conservation of Leontis–Westhof interactions, the tertiary network core building rules apply to all tRNAAsp from mammalian mitochondria. PMID:19767615

  6. MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding.

    PubMed

    Asamitsu, Kaori; Hirokawa, Takatsugu; Okamoto, Takashi

    2017-01-01

    In this study, we applied molecular dynamics (MD) simulation to analyze the dynamic behavior of the Tat/CycT1/CDK9 tri-molecular complex and revealed the structural changes of P-TEFb upon Tat binding. We found that Tat could deliberately change the local flexibility of CycT1. Although the structural coordinates of the H1 and H2 helices did not substantially change, H1', H2', and H3' exhibited significant changes en masse. Consequently, the CycT1 residues involved in Tat binding, namely Tat-recognition residues (TRRs), lost their flexibility with the addition of Tat to P-TEFb. In addition, we clarified the structural variation of CDK9 in complex with CycT1 in the presence or absence of Tat. Interestingly, Tat addition significantly reduced the structural variability of the T-loop, thus consolidating the structural integrity of P-TEFb. Finally, we deciphered the formation of the hidden catalytic cavity of CDK9 upon Tat binding. MD simulation revealed that the PITALRE signature sequence of CDK9 flips the inactive kinase cavity of CDK9 into the active form by connecting with Thr186, which is crucial for its activity, thus presumably recruiting the substrate peptide such as the C-terminal domain of RNA pol II. These findings provide vital information for the development of effective novel anti-HIV drugs with CDK9 catalytic activity as the target.

  7. Bayesian Estimation Supersedes the "t" Test

    ERIC Educational Resources Information Center

    Kruschke, John K.

    2013-01-01

    Bayesian estimation for 2 groups provides complete distributions of credible values for the effect size, group means and their difference, standard deviations and their difference, and the normality of the data. The method handles outliers. The decision rule can accept the null value (unlike traditional "t" tests) when certainty in the estimate is…

  8. Significance testing testate amoeba water table reconstructions

    NASA Astrophysics Data System (ADS)

    Payne, Richard J.; Babeshko, Kirill V.; van Bellen, Simon; Blackford, Jeffrey J.; Booth, Robert K.; Charman, Dan J.; Ellershaw, Megan R.; Gilbert, Daniel; Hughes, Paul D. M.; Jassey, Vincent E. J.; Lamentowicz, Łukasz; Lamentowicz, Mariusz; Malysheva, Elena A.; Mauquoy, Dmitri; Mazei, Yuri; Mitchell, Edward A. D.; Swindles, Graeme T.; Tsyganov, Andrey N.; Turner, T. Edward; Telford, Richard J.

    2016-04-01

    Transfer functions are valuable tools in palaeoecology, but their output may not always be meaningful. A recently-developed statistical test ('randomTF') offers the potential to distinguish among reconstructions which are more likely to be useful, and those less so. We applied this test to a large number of reconstructions of peatland water table depth based on testate amoebae. Contrary to our expectations, a substantial majority (25 of 30) of these reconstructions gave non-significant results (P > 0.05). The underlying reasons for this outcome are unclear. We found no significant correlation between randomTF P-value and transfer function performance, the properties of the training set and reconstruction, or measures of transfer function fit. These results give cause for concern but we believe it would be extremely premature to discount the results of non-significant reconstructions. We stress the need for more critical assessment of transfer function output, replication of results and ecologically-informed interpretation of palaeoecological data.

  9. Test Plan Procedure for Experiment T-003

    DOT National Transportation Integrated Search

    1971-05-19

    This document defines the type, sequence, and procedural details required to perform each test on the T-003 experiment aerosol analyzer, its subsystems and components. This plan utilizes the flexibility allowed for instruments in criticality category...

  10. Clinical significance of Tim3-positive T cell subsets in patients with multiple sclerosis.

    PubMed

    Feng, Xuemei; Feng, Juan

    2016-12-01

    The present study evaluated associations between the percentages of T cell immunoglobulin and mucin domain 3 (Tim3)-positive T cells and related cytokines and multiple sclerosis (MS). We collected peripheral blood samples from 30 MS patients and 30 healthy controls. Flow cytometry was used to determine the proportions of CD3 + Tim3 + , CD4 + Tim3 + , and CD4 + CD25 + Tim3 + in peripheral blood mononuclear cells (PBMCs) and related cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ also were determined using enzyme-linked immunosorbent assays (ELISA). The percentages of Tim3-positive T cells in CD4 + and CD4 + CD25 + T cell subsets were significantly lower among MS patients than among controls. This difference was particularly evident in the CD4 + CD25(high) T cell subset. The proportions of CD4 + Tim3 + and CD4 + CD25 + Tim3 + cells in PBMCs were significantly lower in the MS group than in the control group, whereas no significant differences were detected regarding the percentages of CD3 + Tim3 + in PBMCs and T cell subsets. The serum concentrations of galectin-9, IL-17, and IFN-γ all were increased in MS patients compared with healthy controls. Our results support that Tim3 and related cytokines may be involved in the onset of MS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. [Prostatic granulomas revealing a peripheral T-cell lymphoma].

    PubMed

    Foguem, C; Curlier, E; Rouamba, M-M; Regent, A; Philippe, P

    2009-02-01

    The presence of granulomas on tissue biopsie has been reported in a wide range of disorders. The clinical presentation and the diagnostic work-up of granulomatosis can be difficult as it is illustrated in the following report. A 59-year-old patient was referred in 2002 for a granulomatous prostatitis. Physical examination was normal. Except for the increase of prostate-specific antigen (which motivated a biopsy), the laboratory results were normal. Thoracic CT-scan disclosed mediastinal lymph nodes. A minor salivary gland biopsy was consistent with the diagnosis of sarcoidosis. In 2004, the patient presented an epidermal necrolysis, and in 2005 the deterioration of general status raised suspicion of a lymphoproliferative disorder. Liver and bone marrow biopsies revealed a granulomatous process. Despite steroid therapy, the patient died. Autopsy discloses a anaplasic T cell lymphoma. This report illustrates the relationship between sarcoidosis and lymphoma as a mode of presentation, a complication, or an accidental but misleading association? The association between anaplastic lymphoma and sarcoidosis is exceptional.

  12. Discovery of Highly Potent Tyrosinase Inhibitor, T1, with Significant Anti-Melanogenesis Ability by zebrafish in vivo Assay and Computational Molecular Modeling

    NASA Astrophysics Data System (ADS)

    Chen, Wang-Chuan; Tseng, Tien-Sheng; Hsiao, Nai-Wan; Lin, Yun-Lian; Wen, Zhi-Hong; Tsai, Chin-Chuan; Lee, Yu-Ching; Lin, Hui-Hsiung; Tsai, Keng-Chang

    2015-01-01

    Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 +/- 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.

  13. Patient-Customized Drug Combination Prediction and Testing for T-cell Prolymphocytic Leukemia Patients.

    PubMed

    He, Liye; Tang, Jing; Andersson, Emma I; Timonen, Sanna; Koschmieder, Steffen; Wennerberg, Krister; Mustjoki, Satu; Aittokallio, Tero

    2018-05-01

    The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival pathways are required. Here we implemented a computational-experimental drug combination prediction and testing (DCPT) platform for efficient in silico prioritization and ex vivo testing in patient-derived samples to identify customized synergistic combinations for individual cancer patients. DCPT used drug-target interaction networks to traverse the massive combinatorial search spaces among 218 compounds (a total of 23,653 pairwise combinations) and identified cancer-selective synergies by using differential single-compound sensitivity profiles between patient cells and healthy controls, hence reducing the likelihood of toxic combination effects. A polypharmacology-based machine learning modeling and network visualization made use of baseline genomic and molecular profiles to guide patient-specific combination testing and clinical translation phases. Using T-cell prolymphocytic leukemia (T-PLL) as a first case study, we show how the DCPT platform successfully predicted distinct synergistic combinations for each of the three T-PLL patients, each presenting with different resistance patterns and synergy mechanisms. In total, 10 of 24 (42%) of selective combination predictions were experimentally confirmed to show synergy in patient-derived samples ex vivo The identified selective synergies among approved drugs, including tacrolimus and temsirolimus combined with BCL-2 inhibitor venetoclax, may offer novel drug repurposing opportunities for treating T-PLL. Significance: An integrated use of functional drug screening combined with genomic and molecular profiling enables patient-customized prediction and testing of drug combination synergies for T-PLL patients. Cancer

  14. CAR T-cell therapy for glioblastoma: ready for the next round of clinical testing?

    PubMed

    Prinzing, Brooke L; Gottschalk, Stephen M; Krenciute, Giedre

    2018-05-01

    The outcome for patients with glioblastoma (GBM) remains poor, and there is an urgent need to develop novel therapeutic approaches. T cells genetically modified with chimeric antigen receptors (CARs) hold the promise to improve outcomes since they recognize and kill cells through different mechanisms than conventional therapeutics. Areas covered: This article reviews CAR design, tumor associated antigens expressed by GBMs that can be targeted with CAR T cells, preclinical and clinical studies conducted with CAR T cells, and genetic approaches to enhance their effector function. Expert commentary: While preclinical studies have highlighted the potent anti-GBM activity of CAR T cells, the initial foray of CAR T-cell therapies into the clinic resulted only in limited benefits for GBM patients. Additional genetic modification of CAR T cells has resulted in a significant increase in their anti-GBM activity in preclinical models. We are optimistic that clinical testing of these enhanced CAR T cells will be safe and result in improved anti-glioma activity in GBM patients.

  15. Transcriptome Analysis of CD4+ T Cells in Coeliac Disease Reveals Imprint of BACH2 and IFNγ Regulation

    PubMed Central

    Molloy, Ben; Dominguez Castro, Patricia; Cormican, Paul; Trimble, Valerie; Mahmud, Nasir; McManus, Ross

    2015-01-01

    Genetic studies have to date identified 43 genome wide significant coeliac disease susceptibility (CD) loci comprising over 70 candidate genes. However, how altered regulation of such disease associated genes contributes to CD pathogenesis remains to be elucidated. Recently there has been considerable emphasis on characterising cell type specific and stimulus dependent genetic variants. Therefore in this study we used RNA sequencing to profile over 70 transcriptomes of CD4+ T cells, a cell type crucial for CD pathogenesis, in both stimulated and resting samples from individuals with CD and unaffected controls. We identified extensive transcriptional changes across all conditions, with the previously established CD gene IFNy the most strongly up-regulated gene (log2 fold change 4.6; Padjusted = 2.40x10-11) in CD4+ T cells from CD patients compared to controls. We show a significant correlation of differentially expressed genes with genetic studies of the disease to date (Padjusted = 0.002), and 21 CD candidate susceptibility genes are differentially expressed under one or more of the conditions used in this study. Pathway analysis revealed significant enrichment of immune related processes. Co-expression network analysis identified several modules of coordinately expressed CD genes. Two modules were particularly highly enriched for differentially expressed genes (P<2.2x10-16) and highlighted IFNy and the genetically associated transcription factor BACH2 which showed significantly reduced expression in coeliac samples (log2FC -1.75; Padjusted = 3.6x10-3) as key regulatory genes in CD. Genes regulated by BACH2 were very significantly over-represented among our differentially expressed genes (P<2.2x10-16) indicating that reduced expression of this master regulator of T cell differentiation promotes a pro-inflammatory response and strongly corroborates genetic evidence that BACH2 plays an important role in CD pathogenesis. PMID:26444573

  16. MASH test 3-11 on the Texas T101 bridge rail

    DOT National Transportation Integrated Search

    2011-03-01

    The Texas T101 bridge rail is widely used in the state of Texas. Previous testing demonstrated its ability to contain and redirect passenger cars and a 20,000-lb school bus. Based on this testing, the Federal Highway Administration accepted the T101 ...

  17. Direct Detection of T- and B-Memory Lymphocytes by ImmunoSpot® Assays Reveals HCMV Exposure that Serum Antibodies Fail to Identify.

    PubMed

    Terlutter, Fredrik; Caspell, Richard; Nowacki, Tobias M; Lehmann, Alexander; Li, Ruliang; Zhang, Ting; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

    2018-05-19

    It is essential to identify donors who have not been infected with human cytomegalovirus (HCMV) in order to avoid transmission of HCMV to recipients of blood transfusions or organ transplants. In the present study, we tested the reliability of seronegativity as an indicator for the lack of HCMV exposure in healthy human blood donors. Eighty-two HCMV seronegative individuals were identified, and their peripheral blood mononuclear cells (PBMC) were tested in ImmunoSpot® assays for the presence of HCMV-specific T- and B-memory lymphocytes. Eighty-two percent (67 of 82) of these HCMV seronegative individuals featured at least one memory cell that was lineage specific for HCMV, with the majority of these subjects possessing CD4+ and CD8+ T cells, as well as B cells, providing three independent lines of evidence for having developed immunity to HCMV. Only 15 of these 82 donors (18%) showed neither T- nor B-cell memory to HCMV, consistent with immunological naïveté to the virus. The data suggest that measurements of serum antibodies frequently fail to reveal HCMV exposure in humans, which may be better identified by direct detection of HCMV-specific memory lymphocytes.

  18. T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells

    PubMed Central

    Witkover, Aviva; Tanaka, Yuetsu; Fields, Paul; Bangham, Charles R. M.

    2016-01-01

    There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL) responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1), contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation. It remains unclear whether patients with ATL possess CTLs that can kill the malignant HTLV-1 infected clone. Here we used flow cytometric staining of TCRVβ and cell adhesion molecule-1 (CADM1) to identify monoclonal populations of HTLV-1-infected T cells in the peripheral blood of patients with ATL. Thus, we quantified the rate of CD8+-mediated killing of the putative malignant clone in ex vivo blood samples. We observed that CD8+ cells from ATL patients were unable to lyse autologous ATL clones when tested directly ex vivo. However, short in vitro culture restored the ability of CD8+ cells to kill ex vivo ATL clones in some donors. The capacity of CD8+ cells to lyse HTLV-1 infected cells which expressed the viral sense strand gene products was significantly enhanced after in vitro culture, and donors with an ATL clone that expressed the HTLV-1 Tax gene were most likely to make a detectable lytic CD8+ response to the ATL cells. We conclude that some patients with ATL possess functional tumour-specific CTLs which could be exploited to contribute to control of the disease. PMID:27893842

  19. Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells

    PubMed Central

    Arai, Ayako; Nakazawa, Atsuko; Kawano, Fuyuko; Ichikawa, Sayumi; Shimizu, Norio; Yamamoto, Naoki; Morio, Tomohiro; Ohga, Shouichi; Nakamura, Hiroyuki; Ito, Mamoru; Miura, Osamu; Komano, Jun; Fujiwara, Shigeyoshi

    2011-01-01

    Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases. PMID:22028658

  20. Novel mouse xenograft models reveal a critical role of CD4+ T cells in the proliferation of EBV-infected T and NK cells.

    PubMed

    Imadome, Ken-ichi; Yajima, Misako; Arai, Ayako; Nakazawa, Atsuko; Kawano, Fuyuko; Ichikawa, Sayumi; Shimizu, Norio; Yamamoto, Naoki; Morio, Tomohiro; Ohga, Shouichi; Nakamura, Hiroyuki; Ito, Mamoru; Miura, Osamu; Komano, Jun; Fujiwara, Shigeyoshi

    2011-10-01

    Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγ(null) strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases.

  1. WASP (Write a Scientific Paper) using Excel - 8: t-Tests.

    PubMed

    Grech, Victor

    2018-06-01

    t-Testing is a common component of inferential statistics when comparing two means. This paper explains the central limit theorem and the concept of the null hypothesis as well as types of errors. On the practical side, this paper outlines how different t-tests may be performed in Microsoft Excel, for different purposes, both statically as well as dynamically, with Excel's functions. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Biaxial Testing of 2219-T87 Aluminum Alloy Using Cruciform Specimens

    NASA Technical Reports Server (NTRS)

    Dawicke, D. S.; Pollock, W. D.

    1997-01-01

    A cruciform biaxial test specimen was designed and seven biaxial tensile tests were conducted on 2219-T87 aluminum alloy. An elastic-plastic finite element analysis was used to simulate each tests and predict the yield stresses. The elastic-plastic finite analysis accurately simulated the measured load-strain behavior for each test. The yield stresses predicted by the finite element analyses indicated that the yield behavior of the 2219-T87 aluminum alloy agrees with the von Mises yield criterion.

  3. New signatures of underground nuclear tests revealed by satellite radar interferometry

    USGS Publications Warehouse

    Vincent, P.; Larsen, S.; Galloway, D.; Laczniak, R.J.; Walter, W.R.; Foxall, W.; Zucca, J.J.

    2003-01-01

    New observations of surface displacement caused by past underground nuclear tests at the Nevada Test Site (NTS) are presented using interferometric synthetic aperture radar (InSAR). The InSAR data reveal both coseismic and postseismic subsidence signals that extend one kilometer or more across regardless of whether or not a surface crater was formed from each test. While surface craters and other coseismic surface effects (ground cracks, etc.) may be detectable using high resolution optical or other remote sensing techniques, these broader, more subtle subsidence signals (one to several centimeters distributed over an area 1-2 kilometers across) are not detectable using other methods [Barker et al., 1998]. A time series of interferograms reveal that the postseismic signals develop and persist for months to years after the tests and that different rates and styles of deformation occur depending on the geologic and hydrologic setting and conditions of the local test area.

  4. Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus.

    PubMed

    Zhao, Chen; Mao, Jinghe; Ai, Junmei; Shenwu, Ming; Shi, Tieliu; Zhang, Daqing; Wang, Xiaonan; Wang, Yunliang; Deng, Youping

    2013-01-01

    Insulin resistance is a key element in the pathogenesis of type 2 diabetes mellitus. Plasma free fatty acids were assumed to mediate the insulin resistance, while the relationship between lipid and glucose disposal remains to be demonstrated across liver, skeletal muscle and blood. We profiled both lipidomics and gene expression of 144 total peripheral blood samples, 84 from patients with T2D and 60 from healthy controls. Then, factor and partial least squares models were used to perform a combined analysis of lipidomics and gene expression profiles to uncover the bioprocesses that are associated with lipidomic profiles in type 2 diabetes. According to factor analysis of the lipidomic profile, several species of lipids were found to be correlated with different phenotypes, including diabetes-related C23:2CE, C23:3CE, C23:4CE, ePE36:4, ePE36:5, ePE36:6; race-related (African-American) PI36:1; and sex-related PE34:1 and LPC18:2. The major variance of gene expression profile was not caused by known factors and no significant difference can be directly derived from differential gene expression profile. However, the combination of lipidomic and gene expression analyses allows us to reveal the correlation between the altered lipid profile with significantly enriched pathways, such as one carbon pool by folate, arachidonic acid metabolism, insulin signaling pathway, amino sugar and nucleotide sugar metabolism, propanoate metabolism, and starch and sucrose metabolism. The genes in these pathways showed a good capability to classify diabetes samples. Combined analysis of gene expression and lipidomic profiling reveals type 2 diabetes-associated lipid species and enriched biological pathways in peripheral blood, while gene expression profile does not show direct correlation. Our findings provide a new clue to better understand the mechanism of disordered lipid metabolism in association with type 2 diabetes.

  5. Design and test of a double-nuclear RF coil for 1H MRI and 13C MRSI at 7 T

    NASA Astrophysics Data System (ADS)

    Rutledge, Omar; Kwak, Tiffany; Cao, Peng; Zhang, Xiaoliang

    2016-06-01

    RF coil operation at the ultrahigh field of 7 T is fraught with technical challenges that limit the advancement of novel human in vivo applications at 7 T. In this work, a hybrid technique combining a microstrip transmission line and a lumped-element L-C loop coil to form a double-nuclear RF coil for proton magnetic resonance imaging and carbon magnetic resonance spectroscopy at 7 T was proposed and investigated. Network analysis revealed a high Q-factor and excellent decoupling between the coils. Proton images and localized carbon spectra were acquired with high sensitivity. The successful testing of this novel double-nuclear coil demonstrates the feasibility of this hybrid design for double-nuclear MR imaging and spectroscopy studies at the ultrahigh field of 7 T.

  6. One-sided truncated sequential t-test: application to natural resource sampling

    Treesearch

    Gary W. Fowler; William G. O' Regan

    1974-01-01

    A new procedure for constructing one-sided truncated sequential t-tests and its application to natural resource sampling are described. Monte Carlo procedures were used to develop a series of one-sided truncated sequential t-tests and the associated approximations to the operating characteristic and average sample number functions. Different truncation points and...

  7. Statistical significance test for transition matrices of atmospheric Markov chains

    NASA Technical Reports Server (NTRS)

    Vautard, Robert; Mo, Kingtse C.; Ghil, Michael

    1990-01-01

    Low-frequency variability of large-scale atmospheric dynamics can be represented schematically by a Markov chain of multiple flow regimes. This Markov chain contains useful information for the long-range forecaster, provided that the statistical significance of the associated transition matrix can be reliably tested. Monte Carlo simulation yields a very reliable significance test for the elements of this matrix. The results of this test agree with previously used empirical formulae when each cluster of maps identified as a distinct flow regime is sufficiently large and when they all contain a comparable number of maps. Monte Carlo simulation provides a more reliable way to test the statistical significance of transitions to and from small clusters. It can determine the most likely transitions, as well as the most unlikely ones, with a prescribed level of statistical significance.

  8. The Application of Stress-Relaxation Test to Life Assessment of T911/T22 Weld Metal

    NASA Astrophysics Data System (ADS)

    Cao, Tieshan; Zhao, Jie; Cheng, Congqian; Li, Huifang

    2016-03-01

    A dissimilar weld metal was obtained through submerged arc welding of a T911 steel to a T22 steel, and its creep property was explored by stress-relaxation test assisted by some conventional creep tests. The creep rate information of the stress-relaxation test was compared to the minimum and the average creep rates of the conventional creep test. Log-log graph showed that the creep rate of the stress-relaxation test was in a linear relationship with the minimum creep rate of the conventional creep test. Thus, the creep rate of stress-relaxation test could be used in the Monkman-Grant relation to calculate the rupture life. The creep rate of the stress-relaxation test was similar to the average creep rate, and thereby the rupture life could be evaluated by a method of "time to rupture strain." The results also showed that rupture life which was assessed by the Monkman-Grant relation was more accurate than that obtained through the method of "time to rupture strain."

  9. Spectrum fatigue testing of T-shaped tension clips

    NASA Astrophysics Data System (ADS)

    Palmberg, Bjoern; Wallstenius, Bengt

    1992-12-01

    An investigation of strain distributions during static loading and crack propagation and fatigue lives under spectrum loading of T-shaped tension clips was carried out. Three slightly different, with respect to geometry, T shaped tension clips made of aluminum alloy 7010-T73651 were studied. The type 1 and 4 test specimens were different only with respect to the web thickness of the clamping end. The type 1 and 2 test specimens were different with repect to milled flat circular countersink around the holes in the type 2 specimens and with respect to the radius between the web and foot. The spectrum fatigue loading consisted of a load sequence representative for the wing root, lower side, of a fighter aircraft. Tests were made at two different load levels for each specimen type. The strain measurements show that the countersink in the type 2 specimens increases the stresses in the fatigue critical region. This is also manifested in the spectrum fatigue life results, where type 2 specimens show the shortest fatigue lives. The strain measurements show that the torque used for the bolts in joining two test specimens or one test specimen and a dummy has a rather large impact on the strain in the fatigue region. The strains decrease with increasing torque. The spectrum fatigue loading resulted in approximately an equal number of flights to obtain a 10.0 mm crack for specimens of type 1 and 4. This suggests that the type 1 configuration is superior since the web thickness is smaller for this type as compared to the type 4 specimens. In other words, the type 4 specimens have an unnecessary oversize of the clamping end web thickness.

  10. Quantification of myocardial oxygenation in heart failure using blood-oxygen-level-dependent T2* magnetic resonance imaging: Comparison with cardiopulmonary exercise test.

    PubMed

    Nagao, Michinobu; Yamasaki, Yuzo; Kawanami, Satoshi; Kamitani, Takeshi; Sagiyama, Koji; Higo, Taiki; Ide, Tomomi; Takemura, Atsushi; Ishizaki, Umiko; Fukushima, Kenji; Watanabe, Yuji; Honda, Hiroshi

    2017-06-01

    Quantification of myocardial oxygenation (MO) in heart failure (HF) has been less than satisfactory. This has necessitated the use of invasive techniques to measure MO directly or to determine the oxygen demand during exercise using the cardiopulmonary exercise (CPX) test. We propose a new quantification method for MO using blood-oxygen-level-dependent (BOLD) myocardial T2* magnetic resonance imaging (M-T2* MRI), and investigate its correlation with CPX results. Thirty patients with refractory HF who underwent cardiac MRI and CPX test for heart transplantation, and 24 healthy, age-matched volunteers as controls were enrolled. M-T2* imaging was performed using a 3-Tesla and multi-echo gradient-echo sequence. M-T2* was calculated by fitting the signal intensity data for the mid-left ventricular septum to a decay curve. M-T2* was measured under room-air (T2*-air) and after inhalation of oxygen for 10min at a flow rate of 10L/min (T2*-oxy). MO was defined as the difference between the two values (ΔT2*). Changes in M-T2* at the two conditions and ΔT2* between the two groups were compared. Correlation between ΔT2* and CPX results was analyzed using the Pearson coefficient. T2*-oxy was significantly greater than T2*-air in patients with HF (29.9±7.3ms vs. 26.7±6.0ms, p<0.001), whereas no such difference was observed in controls (25.5±4.0ms vs. 25.4±4.4ms). ΔT2* was significantly greater for patients with HF than for controls (3.2±4.5ms vs. -0.1±1.3ms, p<0.001). A significant correlation between ΔT2* and CPX results (peak VO 2 , r=-0.46, p<0.05; O 2 pulse, r=-0.54, p<0.005) was observed. ΔT2* is increased T2*-oxy is greater in patients with HF, and is correlated with oxygen metabolism during exercise as measured by the CPX test. Hence, ΔT2* can be used as a surrogate marker of MO instead of CPX test. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. EGFR T790M mutation testing within the osimertinib AURA Phase I study.

    PubMed

    Dearden, Simon; Brown, Helen; Jenkins, Suzanne; Thress, Kenneth S; Cantarini, Mireille; Cole, Rebecca; Ranson, Malcolm; Jänne, Pasi A

    2017-07-01

    Reliable epidermal growth factor receptor (EGFR) mutation testing techniques are required to identify eligible patients with EGFR mutation/T790M positive advanced non-small cell lung cancer (NSCLC), for treatment with osimertinib (AZD9291), an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI-sensitizing and T790M resistance mutations over wild-type EGFR. There is no current consensus regarding the best method to detect EGFR T790M mutations. The aim of this study was to describe the concordance between local testing, which used a variety of methods, and central testing, using the cobas ® EGFR Mutation Test, for EGFR-sensitizing mutations and the T790M resistance mutation. Tumor samples were obtained from all patients screened for inclusion onto the osimertinib Phase I expansion component of the AURA Phase I/II study (NCT01802632). Samples underwent central laboratory testing for EGFR-sensitizing mutations and T790M resistance mutation using the cobas ® EGFR Mutation Test. Results were compared with local laboratory test results, based on other testing methodologies including Sanger sequencing, therascreen ® , PNAClamp™, and Sequenom MassARRAY ® . Central laboratory testing was successful in 99% of samples passing histopathology review and testing success rates were comparable across the three central laboratories. Concordance between central and local testing for common sensitizing mutations was high (>98%) and concordance for the T790M mutation was also high (>90%). Tumor heterogeneity, along with other technical factors may have influenced this result. Within the osimertinib AURA Phase I study, EGFR mutation testing across three centralized laboratories using the cobas ® EGFR Mutation Test was feasible and successful, with strong concordance between local and central laboratory results, including for T790M. The cobas ® EGFR Mutation Test has subsequently been approved as the companion diagnostic test for osimertinib in

  12. Testing for significance of phase synchronisation dynamics in the EEG.

    PubMed

    Daly, Ian; Sweeney-Reed, Catherine M; Nasuto, Slawomir J

    2013-06-01

    A number of tests exist to check for statistical significance of phase synchronisation within the Electroencephalogram (EEG); however, the majority suffer from a lack of generality and applicability. They may also fail to account for temporal dynamics in the phase synchronisation, regarding synchronisation as a constant state instead of a dynamical process. Therefore, a novel test is developed for identifying the statistical significance of phase synchronisation based upon a combination of work characterising temporal dynamics of multivariate time-series and Markov modelling. We show how this method is better able to assess the significance of phase synchronisation than a range of commonly used significance tests. We also show how the method may be applied to identify and classify significantly different phase synchronisation dynamics in both univariate and multivariate datasets.

  13. Stress Tests for Chest Pain: When You Need an Imaging Test -- and When You Don't

    MedlinePlus

    ... Resources Adult , Geriatric Stress Tests for Chest Pain Stress Tests for Chest Pain When you need an ... pain isn’t from heart disease. A cardiac stress test makes the heart work hard so your ...

  14. Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme.

    PubMed Central

    Jeruzalmi, D; Steitz, T A

    1998-01-01

    The T7 RNA polymerase-T7 lysozyme complex regulates phage gene expression during infection of Escherichia coli. The 2.8 A crystal structure of the complex reveals that lysozyme binds at a site remote from the polymerase active site, suggesting an indirect mechanism of inhibition. Comparison of the T7 RNA polymerase structure with that of the homologous pol I family of DNA polymerases reveals identities in the catalytic site but also differences specific to RNA polymerase function. The structure of T7 RNA polymerase presented here differs significantly from a previously published structure. Sequence similarities between phage RNA polymerases and those from mitochondria and chloroplasts, when interpreted in the context of our revised model of T7 RNA polymerase, suggest a conserved fold. PMID:9670025

  15. Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes

    NASA Astrophysics Data System (ADS)

    Endy, Drew; You, Lingchong; Yin, John; Molineux, Ian J.

    2000-05-01

    We created a simulation based on experimental data from bacteriophage T7 that computes the developmental cycle of the wild-type phage and also of mutants that have an altered genome order. We used the simulation to compute the fitness of more than 105 mutants. We tested these computations by constructing and experimentally characterizing T7 mutants in which we repositioned gene 1, coding for T7 RNA polymerase. Computed protein synthesis rates for ectopic gene 1 strains were in moderate agreement with observed rates. Computed phage-doubling rates were close to observations for two of four strains, but significantly overestimated those of the other two. Computations indicate that the genome organization of wild-type T7 is nearly optimal for growth: only 2.8% of random genome permutations were computed to grow faster, the highest 31% faster, than wild type. Specific discrepancies between computations and observations suggest that a better understanding of the translation efficiency of individual mRNAs and the functions of qualitatively "nonessential" genes will be needed to improve the T7 simulation. In silico representations of biological systems can serve to assess and advance our understanding of the underlying biology. Iteration between computation, prediction, and observation should increase the rate at which biological hypotheses are formulated and tested.

  16. Structural characterization of ribT from Bacillus subtilis reveals it as a GCN5-related N-acetyltransferase.

    PubMed

    Srivastava, Ritika; Kaur, Amanpreet; Sharma, Charu; Karthikeyan, Subramanian

    2018-04-01

    In bacteria, biosynthesis of riboflavin occurs through a series of enzymatic steps starting with one molecule of GTP and two molecules of ribulose-5-phosphate. In Bacillus subtilis (B. subtilis) the genes (ribD/G, ribE, ribA, ribH and ribT) which are involved in riboflavin biosynthesis are organized in an operon referred as rib operon. All the genes of rib operon are characterized functionally except for ribT. The ribT gene with unknown function is found at the distal terminal of rib operon and annotated as a putative N-acetyltransferase. Here, we report the crystal structure of ribT from B. subtilis (bribT) complexed with coenzyme A (CoA) at 2.1 Å resolution determined by single wavelength anomalous dispersion method. Our structural study reveals that bribT is a member of GCN5-related N-acetyltransferase (GNAT) superfamily and contains all the four conserved structural motifs that have been in other members of GNAT superfamily. The members of GNAT family transfers the acetyl group from acetyl coenzyme A (AcCoA) to a variety of substrates. Moreover, the structural analysis reveals that the residues Glu-67 and Ser-107 are suitably positioned to act as a catalytic base and catalytic acid respectively suggesting that the catalysis by bribT may follow a direct transfer mechanism. Surprisingly, the mutation of a non-conserved amino acid residue Cys-112 to alanine or serine affected the binding of AcCoA to bribT, indicating a possible role of Cys-112 in the catalysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A Spreadsheet Tool for Learning the Multiple Regression F-Test, T-Tests, and Multicollinearity

    ERIC Educational Resources Information Center

    Martin, David

    2008-01-01

    This note presents a spreadsheet tool that allows teachers the opportunity to guide students towards answering on their own questions related to the multiple regression F-test, the t-tests, and multicollinearity. The note demonstrates approaches for using the spreadsheet that might be appropriate for three different levels of statistics classes,…

  18. No Clinically Significant Difference Between Adult and Pediatric IKDC Subjective Knee Evaluation Scores in Adults.

    PubMed

    Stegmeier, Nicole; Oak, Sameer R; O'Rourke, Colin; Strnad, Greg; Spindler, Kurt P; Jones, Morgan; Farrow, Lutul D; Andrish, Jack; Saluan, Paul

    Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Randomized crossover study design. Level 2. The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch's 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R 2 of 92.6%. There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood.

  19. A goodness-of-fit test for capture-recapture model M(t) under closure

    USGS Publications Warehouse

    Stanley, T.R.; Burnham, K.P.

    1999-01-01

    A new, fully efficient goodness-of-fit test for the time-specific closed-population capture-recapture model M(t) is presented. This test is based on the residual distribution of the capture history data given the maximum likelihood parameter estimates under model M(t), is partitioned into informative components, and is based on chi-square statistics. Comparison of this test with Leslie's test (Leslie, 1958, Journal of Animal Ecology 27, 84- 86) for model M(t), using Monte Carlo simulations, shows the new test generally outperforms Leslie's test. The new test is frequently computable when Leslie's test is not, has Type I error rates that are closer to nominal error rates than Leslie's test, and is sensitive to behavioral variation and heterogeneity in capture probabilities. Leslie's test is not sensitive to behavioral variation in capture probabilities but, when computable, has greater power to detect heterogeneity than the new test.

  20. Mapping Human Cortical Areas in vivo Based on Myelin Content as Revealed by T1- and T2-weighted MRI

    PubMed Central

    Glasser, Matthew F.; Van Essen, David C.

    2011-01-01

    Non-invasively mapping the layout of cortical areas in humans is a continuing challenge for neuroscience. We present a new method of mapping cortical areas based on myelin content as revealed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The method is generalizable across different 3T scanners and pulse sequences. We use the ratio of T1w/T2w image intensities to eliminate the MR-related image intensity bias and enhance the contrast to noise ratio for myelin. Data from each subject was mapped to the cortical surface and aligned across individuals using surface-based registration. The spatial gradient of the group average myelin map provides an observer-independent measure of sharp transitions in myelin content across the surface—i.e. putative cortical areal borders. We found excellent agreement between the gradients of the myelin maps and the gradients of published probabilistic cytoarchitectonically defined cortical areas that were registered to the same surface-based atlas. For other cortical regions, we used published anatomical and functional information to make putative identifications of dozens of cortical areas or candidate areas. In general, primary and early unimodal association cortices are heavily myelinated and higher, multi-modal, association cortices are more lightly myelinated, but there are notable exceptions in the literature that are confirmed by our results. The overall pattern in the myelin maps also has important correlations with the developmental onset of subcortical white matter myelination, evolutionary cortical areal expansion in humans compared to macaques, postnatal cortical expansion in humans, and maps of neuronal density in non-human primates. PMID:21832190

  1. Experimental parametric studies of transonic T-tail flutter. [wind tunnel tests

    NASA Technical Reports Server (NTRS)

    Ruhlin, C. L.; Sandford, M. C.

    1975-01-01

    Wind-tunnel tests of the T-tail of a wide-body jet airplane were made at Mach numbers up to 1.02. The model consisted of a 1/13-size scaled version of the T-tail, fuselage, and inboard wing of the airplane. Two interchangeable T-tails were tested, one with design stiffness for flutter-clearance studies and one with reduced stiffness for flutter-trend studies. Transonic antisymmetric-flutter boundaries were determined for the models with variations in: (1) fin-spar stiffness, (2) stabilizer dihedral angle (-5 deg and 0 deg), (3) wing and forward-fuselage shape, and (4) nose shape of the fin-stabilizer juncture. A transonic symmetric-flutter boundary and flutter trends were established for variations in stabilizer pitch stiffness. Photographs of the test configurations are shown.

  2. Experiment K-6-16. Morphological examination of rat testes. The effect of Cosmos 1887 flight on spermatogonial population and testosterone level in rat testes

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Kato, K.; Stevenson, J.; Vasques, M.; Sapp, W.; Williams, C.; Popova, I. A.; Serova, L. V.

    1990-01-01

    Testes from rats flown on Cosmos 1887 for twelve and a half days were compared to basal control, synchronous control and vivarium maintained rats. When the mean weights of flight testes, normalized for weight/100 gms, were compared to the vivarium controls they were 6.7 percent lighter. Although the flight testes were lighter than the synchronous, the difference is not significant. Counts of spermatogonial cells from 5 animals in each group revealed a 4 percent decrease in flight compared to vivarium controls. In both cases the t-Test significance was less than 0.02. The serum testosterone levels of all animals (flight, synchronous and vivarium) were significantly below the basal controls.

  3. SU-E-T-769: T-Test Based Prior Error Estimate and Stopping Criterion for Monte Carlo Dose Calculation in Proton Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hong, X; Gao, H; Schuemann, J

    2015-06-15

    Purpose: The Monte Carlo (MC) method is a gold standard for dose calculation in radiotherapy. However, it is not a priori clear how many particles need to be simulated to achieve a given dose accuracy. Prior error estimate and stopping criterion are not well established for MC. This work aims to fill this gap. Methods: Due to the statistical nature of MC, our approach is based on one-sample t-test. We design the prior error estimate method based on the t-test, and then use this t-test based error estimate for developing a simulation stopping criterion. The three major components are asmore » follows.First, the source particles are randomized in energy, space and angle, so that the dose deposition from a particle to the voxel is independent and identically distributed (i.i.d.).Second, a sample under consideration in the t-test is the mean value of dose deposition to the voxel by sufficiently large number of source particles. Then according to central limit theorem, the sample as the mean value of i.i.d. variables is normally distributed with the expectation equal to the true deposited dose.Third, the t-test is performed with the null hypothesis that the difference between sample expectation (the same as true deposited dose) and on-the-fly calculated mean sample dose from MC is larger than a given error threshold, in addition to which users have the freedom to specify confidence probability and region of interest in the t-test based stopping criterion. Results: The method is validated for proton dose calculation. The difference between the MC Result based on the t-test prior error estimate and the statistical Result by repeating numerous MC simulations is within 1%. Conclusion: The t-test based prior error estimate and stopping criterion are developed for MC and validated for proton dose calculation. Xiang Hong and Hao Gao were partially supported by the NSFC (#11405105), the 973 Program (#2015CB856000) and the Shanghai Pujiang Talent Program (#14PJ1404500)« less

  4. Test Design Considerations for Students with Significant Cognitive Disabilities

    ERIC Educational Resources Information Center

    Anderson, Daniel; Farley, Dan; Tindal, Gerald

    2015-01-01

    Students with significant cognitive disabilities present an assessment dilemma that centers on access and validity in large-scale testing programs. Typically, access is improved by eliminating construct-irrelevant barriers, while validity is improved, in part, through test standardization. In this article, one state's alternate assessment data…

  5. Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing

    PubMed Central

    Nkurunungi, Gyaviira; Lutangira, Jimreeves E.; Lule, Swaib A.; Akurut, Hellen; Kizindo, Robert; Fitchett, Joseph R.; Kizito, Dennison; Sebina, Ismail; Muhangi, Lawrence; Webb, Emily L.; Cose, Stephen; Elliott, Alison M.

    2012-01-01

    Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of

  6. Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study.

    PubMed

    Koskela, J; Laiho, J; KäHönen, M; Rontu, R; Lehtinen, R; Viik, J; Niemi, M; Niemelä, K; Kööbi, T; Turjanmaa, V; Pörsti, I; Lehtimäki, T; Nieminen, T

    2008-01-01

    Cardiac repolarization is regulated, in part, by the KCNH2 gene, which encodes a rapidly activating component of the delayed rectifier potassium channel. The gene expresses a functional single nucleotide polymorphism, K897T, which changes the biophysical properties of the channel. The objective of this study was to evaluate whether this polymorphism influences two indices of repolarization--the QT interval and T-wave alternans (TWA)--during different phases of a physical exercise test. The cohort consisted of 1,975 patients undergoing an exercise test during which on-line electrocardiographic data were registered. Information on coronary risk factors and medication was recorded. The 2690A>C nucleotide variation in the KCNH2 gene corresponding to the K897T amino acid change was analysed after polymerase chain reaction with allele-specific TaqMan probes. Among all subjects, the QTc intervals did not differ between the three genotype groups (p> or =0.31, RANOVA). Women with the CC genotype tended to have longer QT intervals during the exercise test, but the difference was statistically significant only at rest (p = 0.011, ANOVA). This difference was also detected when the analysis was adjusted for several factors influencing the QT interval. No statistically significant effects of the K897T polymorphism on TWA were observed among all subjects (p = 0.16, RANOVA), nor in men and women separately. The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the TWA, but the influence of the CC genotype on QT interval deserves further research among women.

  7. Your Chi-Square Test Is Statistically Significant: Now What?

    ERIC Educational Resources Information Center

    Sharpe, Donald

    2015-01-01

    Applied researchers have employed chi-square tests for more than one hundred years. This paper addresses the question of how one should follow a statistically significant chi-square test result in order to determine the source of that result. Four approaches were evaluated: calculating residuals, comparing cells, ransacking, and partitioning. Data…

  8. A closer look at the effect of preliminary goodness-of-fit testing for normality for the one-sample t-test.

    PubMed

    Rochon, Justine; Kieser, Meinhard

    2011-11-01

    Student's one-sample t-test is a commonly used method when inference about the population mean is made. As advocated in textbooks and articles, the assumption of normality is often checked by a preliminary goodness-of-fit (GOF) test. In a paper recently published by Schucany and Ng it was shown that, for the uniform distribution, screening of samples by a pretest for normality leads to a more conservative conditional Type I error rate than application of the one-sample t-test without preliminary GOF test. In contrast, for the exponential distribution, the conditional level is even more elevated than the Type I error rate of the t-test without pretest. We examine the reasons behind these characteristics. In a simulation study, samples drawn from the exponential, lognormal, uniform, Student's t-distribution with 2 degrees of freedom (t(2) ) and the standard normal distribution that had passed normality screening, as well as the ingredients of the test statistics calculated from these samples, are investigated. For non-normal distributions, we found that preliminary testing for normality may change the distribution of means and standard deviations of the selected samples as well as the correlation between them (if the underlying distribution is non-symmetric), thus leading to altered distributions of the resulting test statistics. It is shown that for skewed distributions the excess in Type I error rate may be even more pronounced when testing one-sided hypotheses. ©2010 The British Psychological Society.

  9. Using the Student's "t"-Test with Extremely Small Sample Sizes

    ERIC Educational Resources Information Center

    de Winter, J. C .F.

    2013-01-01

    Researchers occasionally have to work with an extremely small sample size, defined herein as "N" less than or equal to 5. Some methodologists have cautioned against using the "t"-test when the sample size is extremely small, whereas others have suggested that using the "t"-test is feasible in such a case. The present…

  10. Characterisation of the clinical and activated T cell response to repeat delayed-type hypersensitivity skin challenges in human subjects, with KLH and PPD, as a potential model to test T cell-targeted therapies.

    PubMed

    Belson, Alexandra; Schmidt, Tim; Fernando, Disala; Hardes, Kelly; Scott, Nicola; Brett, Sara; Clark, Deborah; Oliveira, João Joaquim; Davis, Bill; McHugh, Simon; Stone, John

    2016-05-01

    To characterise the delayed-type hypersensitivity (DTH) skin reaction to repeated challenges of keyhole limpet hemocyanin (KLH) and tuberculin purified protein derivative (PPD) in healthy volunteers, as a potential model to test T cell-targeted investigational agents. Forty-nine subjects received either KLH, PPD, or PBS repeat skin challenges, and clinical assessments including induration, erythema and Laser Doppler Imaging. Skin biopsies or suction blisters were taken after challenge to investigate the cellular infiltrate of the challenge site, the T cell activation status, as determined by LAG-3 expression, and, specifically for the blister, the concentrations of inflammatory cytokines. Point estimates, estimates of variation and corresponding 95% confidence intervals were constructed for each type of challenge and timepoint. The DTH response could be measured at 48 and 120 h post-KLH and PPD challenge with induration, erythema and Laser Doppler Imaging, with 48 h post-challenge demonstrating the peak of the response. PPD was well tolerated in subjects after multiple challenges, however, a significant number of KLH-treated subjects demonstrated an injection site reaction 6-7 days following the SC injection. PPD demonstrated a boost effect on the second challenge as measured by increased induration, where as this was not noted consistently for KLH. Compared to unchallenged and PBS control-injected skin, increased T cell numbers were detected in the challenge site by both the skin suction blister and biopsy technique, at either time point following KLH or PPD challenge. Use of the T cell activation marker LAG-3 demonstrated the activated phenotype of these cells. In skin blisters, higher numbers of LAG-3+ T cells were detected at 48 h post-challenge, whereas in the biopsies, similar numbers of LAG-3+ cells were observed at both 48 and 120 h. Analysis of blister T cell subpopulations revealed some differences in phenotypes between the time points and between the CD4

  11. 46 CFR 35.20-10 - Steering gear test-T/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Steering gear test-T/ALL. 35.20-10 Section 35.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS OPERATIONS Navigation § 35.20-10 Steering gear test—T/ALL. On all tankships making voyages of more than 48 hours' duration, the entire...

  12. 46 CFR 35.20-10 - Steering gear test-T/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Steering gear test-T/ALL. 35.20-10 Section 35.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS OPERATIONS Navigation § 35.20-10 Steering gear test—T/ALL. On all tankships making voyages of more than 48 hours' duration, the entire...

  13. Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

    PubMed Central

    Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J.; Tooney, Paul A.; Scott, Rodney J.; Carr, Vaughan J.; Cairns, Murray J.

    2012-01-01

    Background While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. Methodology/Principal Findings The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene. Conclusions This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. PMID:22558445

  14. Complete mitochondrial genomes of Taenia multiceps, T. hydatigena and T. pisiformis: additional molecular markers for a tapeworm genus of human and animal health significance.

    PubMed

    Jia, Wan-Zhong; Yan, Hong-Bin; Guo, Ai-Jiang; Zhu, Xing-Quan; Wang, Yu-Chao; Shi, Wan-Gui; Chen, Hao-Tai; Zhan, Fang; Zhang, Shao-Hua; Fu, Bao-Quan; Littlewood, D Timothy J; Cai, Xue-Peng

    2010-07-22

    Mitochondrial genomes provide a rich source of molecular variation of proven and widespread utility in molecular ecology, population genetics and evolutionary biology. The tapeworm genus Taenia includes a diversity of tapeworm parasites of significant human and veterinary importance. Here we add complete sequences of the mt genomes of T. multiceps, T. hydatigena and T. pisiformis, to a data set of 4 published mtDNAs in the same genus. Seven complete mt genomes of Taenia species are used to compare and contrast variation within and between genomes in the genus, to estimate a phylogeny for the genus, and to develop novel molecular markers as part of an extended mitochondrial toolkit. The complete circular mtDNAs of T. multiceps, T. hydatigena and T. pisiformis were 13,693, 13,492 and 13,387 bp in size respectively, comprising the usual complement of flatworm genes. Start and stop codons of protein coding genes included those found commonly amongst other platyhelminth mt genomes, but the much rarer initiation codon GTT was inferred for the gene atp6 in T. pisiformis. Phylogenetic analysis of mtDNAs offered novel estimates of the interrelationships of Taenia. Sliding window analyses showed nad6, nad5, atp6, nad3 and nad2 are amongst the most variable of genes per unit length, with the highest peaks in nucleotide diversity found in nad5. New primer pairs capable of amplifying fragments of variable DNA in nad1, rrnS and nad5 genes were designed in silico and tested as possible alternatives to existing mitochondrial markers for Taenia. With the availability of complete mtDNAs of 7 Taenia species, we have shown that analysis of amino acids provides a robust estimate of phylogeny for the genus that differs markedly from morphological estimates or those using partial genes; with implications for understanding the evolutionary radiation of important Taenia. Full alignment of the nucleotides of Taenia mtDNAs and sliding window analysis suggests numerous alternative gene

  15. Complete mitochondrial genomes of Taenia multiceps, T. hydatigena and T. pisiformis: additional molecular markers for a tapeworm genus of human and animal health significance

    PubMed Central

    2010-01-01

    Background Mitochondrial genomes provide a rich source of molecular variation of proven and widespread utility in molecular ecology, population genetics and evolutionary biology. The tapeworm genus Taenia includes a diversity of tapeworm parasites of significant human and veterinary importance. Here we add complete sequences of the mt genomes of T. multiceps, T. hydatigena and T. pisiformis, to a data set of 4 published mtDNAs in the same genus. Seven complete mt genomes of Taenia species are used to compare and contrast variation within and between genomes in the genus, to estimate a phylogeny for the genus, and to develop novel molecular markers as part of an extended mitochondrial toolkit. Results The complete circular mtDNAs of T. multiceps, T. hydatigena and T. pisiformis were 13,693, 13,492 and 13,387 bp in size respectively, comprising the usual complement of flatworm genes. Start and stop codons of protein coding genes included those found commonly amongst other platyhelminth mt genomes, but the much rarer initiation codon GTT was inferred for the gene atp6 in T. pisiformis. Phylogenetic analysis of mtDNAs offered novel estimates of the interrelationships of Taenia. Sliding window analyses showed nad6, nad5, atp6, nad3 and nad2 are amongst the most variable of genes per unit length, with the highest peaks in nucleotide diversity found in nad5. New primer pairs capable of amplifying fragments of variable DNA in nad1, rrnS and nad5 genes were designed in silico and tested as possible alternatives to existing mitochondrial markers for Taenia. Conclusions With the availability of complete mtDNAs of 7 Taenia species, we have shown that analysis of amino acids provides a robust estimate of phylogeny for the genus that differs markedly from morphological estimates or those using partial genes; with implications for understanding the evolutionary radiation of important Taenia. Full alignment of the nucleotides of Taenia mtDNAs and sliding window analysis suggests

  16. Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies

    PubMed Central

    Tanaka, Tomoyuki; Nakajima-Takagi, Yaeko; Tara, Shiro; Saraya, Atsunori; Koide, Shuhei; Si, Sha; Manabe, Ichiro; Sanada, Masashi; Nakayama, Manabu; Masuko, Masayoshi; Sone, Hirohito

    2017-01-01

    Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR); however, its tumor suppressor function remains largely uncharacterized. We generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain. Although the deletion of exon 4 in male mice (BcorΔE4/y) compromised the repopulating capacity of hematopoietic stem cells, BcorΔE4/y thymocytes had augmented proliferative capacity in culture and showed a strong propensity to induce acute T-cell lymphoblastic leukemia (T-ALL), mostly in a Notch-dependent manner. Myc, one of the critical NOTCH1 targets in T-ALL, was highly up-regulated in BcorΔE4/y T-ALL cells. Chromatin immunoprecipitation/DNA sequencing analysis revealed that BCOR was recruited to the Myc promoter and restrained its activation in thymocytes. BCOR also targeted other NOTCH1 targets and potentially antagonized their transcriptional activation. Bcl6-deficient thymocytes behaved in a manner similar to BcorΔE4/y thymocytes. Our results provide the first evidence of a tumor suppressor role for BCOR in the pathogenesis of T lymphocyte malignancies. PMID:28827447

  17. Creep Tests and Modeling Based on Continuum Damage Mechanics for T91 and T92 Steels

    NASA Astrophysics Data System (ADS)

    Pan, J. P.; Tu, S. H.; Zhu, X. W.; Tan, L. J.; Hu, B.; Wang, Q.

    2017-12-01

    9-11%Cr ferritic steels play an important role in high-temperature and high-pressure boilers of advanced power plants. In this paper, a continuum damage mechanics (CDM)-based creep model was proposed to study the creep behavior of T91 and T92 steels at high temperatures. Long-time creep tests were performed for both steels under different conditions. The creep rupture data and creep curves obtained from creep tests were captured well by theoretical calculation based on the CDM model over a long creep time. It is shown that the developed model is able to predict creep data for the two ferritic steels accurately up to tens of thousands of hours.

  18. Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

    PubMed Central

    Paumier, Katrina L.; Sukoff Rizzo, Stacey J.; Berger, Zdenek; Chen, Yi; Gonzales, Cathleen; Kaftan, Edward; Li, Li; Lotarski, Susan; Monaghan, Michael; Shen, Wei; Stolyar, Polina; Vasilyev, Dmytro; Zaleska, Margaret; D. Hirst, Warren; Dunlop, John

    2013-01-01

    Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1–2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments

  19. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Taxvig, Camilla, E-mail: camta@food.dtu.dk; Olesen, Pelle Thonning; Nellemann, Christine

    2011-02-01

    Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenousmore » metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.« less

  20. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay.

    PubMed

    Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine

    2011-02-01

    Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. 46 CFR 35.20-10 - Steering gear test-T/ALL.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Steering gear test-T/ALL. 35.20-10 Section 35.20-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS OPERATIONS Navigation § 35.20-10 Steering gear test—T/ALL. On all tankships making voyages of more than 48 hours' duration, the entire steering gear, the whistle, the means of...

  2. Manipulating the Alpha Level Cannot Cure Significance Testing.

    PubMed

    Trafimow, David; Amrhein, Valentin; Areshenkoff, Corson N; Barrera-Causil, Carlos J; Beh, Eric J; Bilgiç, Yusuf K; Bono, Roser; Bradley, Michael T; Briggs, William M; Cepeda-Freyre, Héctor A; Chaigneau, Sergio E; Ciocca, Daniel R; Correa, Juan C; Cousineau, Denis; de Boer, Michiel R; Dhar, Subhra S; Dolgov, Igor; Gómez-Benito, Juana; Grendar, Marian; Grice, James W; Guerrero-Gimenez, Martin E; Gutiérrez, Andrés; Huedo-Medina, Tania B; Jaffe, Klaus; Janyan, Armina; Karimnezhad, Ali; Korner-Nievergelt, Fränzi; Kosugi, Koji; Lachmair, Martin; Ledesma, Rubén D; Limongi, Roberto; Liuzza, Marco T; Lombardo, Rosaria; Marks, Michael J; Meinlschmidt, Gunther; Nalborczyk, Ladislas; Nguyen, Hung T; Ospina, Raydonal; Perezgonzalez, Jose D; Pfister, Roland; Rahona, Juan J; Rodríguez-Medina, David A; Romão, Xavier; Ruiz-Fernández, Susana; Suarez, Isabel; Tegethoff, Marion; Tejo, Mauricio; van de Schoot, Rens; Vankov, Ivan I; Velasco-Forero, Santiago; Wang, Tonghui; Yamada, Yuki; Zoppino, Felipe C M; Marmolejo-Ramos, Fernando

    2018-01-01

    We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p -value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.

  3. A close examination of double filtering with fold change and t test in microarray analysis

    PubMed Central

    2009-01-01

    Background Many researchers use the double filtering procedure with fold change and t test to identify differentially expressed genes, in the hope that the double filtering will provide extra confidence in the results. Due to its simplicity, the double filtering procedure has been popular with applied researchers despite the development of more sophisticated methods. Results This paper, for the first time to our knowledge, provides theoretical insight on the drawback of the double filtering procedure. We show that fold change assumes all genes to have a common variance while t statistic assumes gene-specific variances. The two statistics are based on contradicting assumptions. Under the assumption that gene variances arise from a mixture of a common variance and gene-specific variances, we develop the theoretically most powerful likelihood ratio test statistic. We further demonstrate that the posterior inference based on a Bayesian mixture model and the widely used significance analysis of microarrays (SAM) statistic are better approximations to the likelihood ratio test than the double filtering procedure. Conclusion We demonstrate through hypothesis testing theory, simulation studies and real data examples, that well constructed shrinkage testing methods, which can be united under the mixture gene variance assumption, can considerably outperform the double filtering procedure. PMID:19995439

  4. 4. Exterior view of Components Test Laboratory (T27), looking northeast. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Exterior view of Components Test Laboratory (T-27), looking northeast. The building wing on the left houses Test Cell 8 (oxidizer) and the oxidizer storage pit or vault, and that on the right houses Test Cell 10 (environmental). - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  5. 5. Exterior view of Components Test Laboratory (T27), looking northwest. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Exterior view of Components Test Laboratory (T-27), looking northwest. The building wing on the left houses Test Cell 10 (environmental), and that on the right houses Test Cell 9 (fuel) and the fuel storage pit or vault. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  6. Hybrid flower pollination algorithm strategies for t-way test suite generation.

    PubMed

    Nasser, Abdullah B; Zamli, Kamal Z; Alsewari, AbdulRahman A; Ahmed, Bestoun S

    2018-01-01

    The application of meta-heuristic algorithms for t-way testing has recently become prevalent. Consequently, many useful meta-heuristic algorithms have been developed on the basis of the implementation of t-way strategies (where t indicates the interaction strength). Mixed results have been reported in the literature to highlight the fact that no single strategy appears to be superior compared with other configurations. The hybridization of two or more algorithms can enhance the overall search capabilities, that is, by compensating the limitation of one algorithm with the strength of others. Thus, hybrid variants of the flower pollination algorithm (FPA) are proposed in the current work. Four hybrid variants of FPA are considered by combining FPA with other algorithmic components. The experimental results demonstrate that FPA hybrids overcome the problems of slow convergence in the original FPA and offers statistically superior performance compared with existing t-way strategies in terms of test suite size.

  7. Hybrid flower pollination algorithm strategies for t-way test suite generation

    PubMed Central

    Zamli, Kamal Z.; Alsewari, AbdulRahman A.

    2018-01-01

    The application of meta-heuristic algorithms for t-way testing has recently become prevalent. Consequently, many useful meta-heuristic algorithms have been developed on the basis of the implementation of t-way strategies (where t indicates the interaction strength). Mixed results have been reported in the literature to highlight the fact that no single strategy appears to be superior compared with other configurations. The hybridization of two or more algorithms can enhance the overall search capabilities, that is, by compensating the limitation of one algorithm with the strength of others. Thus, hybrid variants of the flower pollination algorithm (FPA) are proposed in the current work. Four hybrid variants of FPA are considered by combining FPA with other algorithmic components. The experimental results demonstrate that FPA hybrids overcome the problems of slow convergence in the original FPA and offers statistically superior performance compared with existing t-way strategies in terms of test suite size. PMID:29718918

  8. The Use of Meta-Analytic Statistical Significance Testing

    ERIC Educational Resources Information Center

    Polanin, Joshua R.; Pigott, Terri D.

    2015-01-01

    Meta-analysis multiplicity, the concept of conducting multiple tests of statistical significance within one review, is an underdeveloped literature. We address this issue by considering how Type I errors can impact meta-analytic results, suggest how statistical power may be affected through the use of multiplicity corrections, and propose how…

  9. Targeted Resequencing and Functional Testing Identifies Low-Frequency Missense Variants in the Gene Encoding GARP as Significant Contributors to Atopic Dermatitis Risk.

    PubMed

    Manz, Judith; Rodríguez, Elke; ElSharawy, Abdou; Oesau, Eva-Maria; Petersen, Britt-Sabina; Baurecht, Hansjörg; Mayr, Gabriele; Weber, Susanne; Harder, Jürgen; Reischl, Eva; Schwarz, Agatha; Novak, Natalija; Franke, Andre; Weidinger, Stephan

    2016-12-01

    Gene-mapping studies have consistently identified a susceptibility locus for atopic dermatitis and other inflammatory diseases on chromosome band 11q13.5, with the strongest association observed for a common variant located in an intergenic region between the two annotated genes C11orf30 and LRRC32. Using a targeted resequencing approach we identified low-frequency and rare missense mutations within the LRRC32 gene encoding the protein GARP, a receptor on activated regulatory T cells that binds latent transforming growth factor-β. Subsequent association testing in more than 2,000 atopic dermatitis patients and 2,000 control subjects showed a significant excess of these LRRC32 variants in individuals with atopic dermatitis. Structural protein modeling and bioinformatic analysis predicted a disruption of protein transport upon these variants, and overexpression assays in CD4 + CD25 - T cells showed a significant reduction in surface expression of the mutated protein. Consistently, flow cytometric (FACS) analyses of different T-cell subtypes obtained from atopic dermatitis patients showed a significantly reduced surface expression of GARP and a reduced conversion of CD4 + CD25 - T cells into regulatory T cells, along with lower expression of latency-associated protein upon stimulation in carriers of the LRRC32 A407T variant. These results link inherited disturbances of transforming growth factor-β signaling with atopic dermatitis risk. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Significance of deep T-wave inversions in asymptomatic athletes with normal cardiovascular examinations: practical solutions for managing the diagnostic conundrum

    PubMed Central

    Wilson, M G; Sharma, S; Carré, F; Charron, P; Richard, P; O'Hanlon, R; Prasad, S K; Heidbuchel, H; Brugada, J; Salah, O; Sheppard, M; George, K P; Whyte, G; Hamilton, B; Chalabi, H

    2012-01-01

    Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts. PMID:23097480

  11. Significance of deep T-wave inversions in asymptomatic athletes with normal cardiovascular examinations: practical solutions for managing the diagnostic conundrum.

    PubMed

    Wilson, M G; Sharma, S; Carré, F; Charron, P; Richard, P; O'Hanlon, R; Prasad, S K; Heidbuchel, H; Brugada, J; Salah, O; Sheppard, M; George, K P; Whyte, G; Hamilton, B; Chalabi, H

    2012-11-01

    Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥ 2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts.

  12. Tension and Bending Testing of an Integral T-Cap for Stitched Composite Airframe Joints

    NASA Technical Reports Server (NTRS)

    Lovejoy, Andrew E.; Leone, Frank A., Jr.

    2016-01-01

    The Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) is a structural concept that was developed by The Boeing Company to address the complex structural design aspects associated with a pressurized hybrid wing body aircraft configuration. An important design feature required for assembly is the integrally stitched T-cap, which provides connectivity of the corner (orthogonal) joint between adjacent panels. A series of tests were conducted on T-cap test articles, with and without a rod stiffener penetrating the T-cap web, under tension (pull-off) and bending loads. Three designs were tested, including the baseline design used in large-scale test articles. The baseline had only the manufacturing stitch row adjacent to the fillet at the base of the T-cap web. Two new designs added stitching rows to the T-cap web at either 0.5- or 1.0-inch spacing along the height of the web. Testing was conducted at NASA Langley Research Center to determine the behavior of the T-cap region resulting from the applied loading. Results show that stitching arrests the initial delamination failures so that the maximum strength capability exceeds the load at which the initial delaminations develop. However, it was seen that the added web stitching had very little effect on the initial delamination failure load, but actually decreased the initial delamination failure load for tension loading of test articles without a stiffener passing through the web. Additionally, the added web stitching only increased the maximum load capability by between 1% and 12.5%. The presence of the stiffener, however, did increase the initial and maximum loads for both tension and bending loading as compared to the stringerless baseline design. Based on the results of the few samples tested, the additional stitching in the T-cap web showed little advantage over the baseline design in terms of structural failure at the T-cap web/skin junction for the current test articles.

  13. Significance of serum total prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer.

    PubMed

    Abdrabo, Abdelkarim A; Fadlalla, Adil I; Fadl-Elmula, Imad M

    2011-11-01

    To assess the significance of serum total prostate specific antigen (tPSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer (PC). One hundred and eighteen patients with serum tPSA ranging between 2.5 and 10 ng/ml with lower urinary tract symptoms presented at the Urology Clinic of Soba University Hospital, Khartoum, Sudan from August 2008 and January 2010 were included in the study. Serum tPSA was measured using enzyme immunoassay method, and accordingly, the patients were classified into 2 groups: patients that had tPSA between 2.5-4.0 ng/ml; and patients that had tPSA between 4.1-10 ng/ml. The DRE was performed on all patients by a qualified urologist, and were recorded as a group with suspicion of PC, and a group with no suspicion of PC. All patients underwent transrectal sextant prostate biopsy. The DRE alone showed 63.8% sensitivity and 68% specificity with 46.9% positive predictive value (PPV) for the diagnosis of PC. The tPSA test revealed 91.6% sensitivity and 24% specificity with PPV of 34%. However, when combining DRE and tPSA, the sensitivity reached 100% and the specificity increased to 92% with PPV of 49%. Combining DRE and tPSA test increases the sensitivity, specificity, and PPV of PC detection.

  14. The "Don't Know" Option in Progress Testing

    ERIC Educational Resources Information Center

    Ravesloot, C. J.; Van der Schaaf, M. F.; Muijtjens, A. M. M.; Haaring, C.; Kruitwagen, C. L. J. J.; Beek, F. J. A.; Bakker, J.; Van Schaik, J.P.J.; Ten Cate, Th. J.

    2015-01-01

    Formula scoring (FS) is the use of a don't know option (DKO) with subtraction of points for wrong answers. Its effect on construct validity and reliability of progress test scores, is subject of discussion. Choosing a DKO may not only be affected by knowledge level, but also by risk taking tendency, and may thus introduce construct-irrelevant…

  15. Significance testing - are we ready yet to abandon its use?

    PubMed

    The, Bertram

    2011-11-01

    Understanding of the damaging effects of significance testing has steadily grown. Reporting p values without dichotomizing the result to be significant or not, is not the solution. Confidence intervals are better, but are troubled by a non-intuitive interpretation, and are often misused just to see whether the null value lies within the interval. Bayesian statistics provide an alternative which solves most of these problems. Although criticized for relying on subjective models, the interpretation of a Bayesian posterior probability is more intuitive than the interpretation of a p value, and seems to be closest to intuitive patterns of human decision making. Another alternative could be using confidence interval functions (or p value functions) to display a continuum of intervals at different levels of confidence around a point estimate. Thus, better alternatives to significance testing exist. The reluctance to abandon this practice might be both preference of clinging to old habits as well as the unfamiliarity with better methods. Authors might question if using less commonly exercised, though superior, techniques will be well received by the editors, reviewers and the readership. A joint effort will be needed to abandon significance testing in clinical research in the future.

  16. Development of diagnostic test instruments to reveal level student conception in kinematic and dynamics

    NASA Astrophysics Data System (ADS)

    Handhika, J.; Cari, C.; Suparmi, A.; Sunarno, W.; Purwandari, P.

    2018-03-01

    The purpose of this research was to develop a diagnostic test instrument to reveal students' conceptions in kinematics and dynamics. The diagnostic test was developed based on the content indicator the concept of (1) displacement and distance, (2) instantaneous and average velocity, (3) zero and constant acceleration, (4) gravitational acceleration (5) Newton's first Law, (6) and Newton's third Law. The diagnostic test development model includes: Diagnostic test requirement analysis, formulating test-making objectives, developing tests, checking the validity of the content and the performance of reliability, and application of tests. The Content Validation Index (CVI) results in the category are highly relevant, with a value of 0.85. Three questions get negative Content Validation Ratio CVR) (-0.6), after revised distractors and clarify visual presentation; the CVR become 1 (highly relevant). This test was applied, obtained 16 valid test items, with Cronbach Alpha value of 0.80. It can conclude that diagnostic test can be used to reveal the level of students conception in kinematics and dynamics.

  17. Manipulating the Alpha Level Cannot Cure Significance Testing

    PubMed Central

    Trafimow, David; Amrhein, Valentin; Areshenkoff, Corson N.; Barrera-Causil, Carlos J.; Beh, Eric J.; Bilgiç, Yusuf K.; Bono, Roser; Bradley, Michael T.; Briggs, William M.; Cepeda-Freyre, Héctor A.; Chaigneau, Sergio E.; Ciocca, Daniel R.; Correa, Juan C.; Cousineau, Denis; de Boer, Michiel R.; Dhar, Subhra S.; Dolgov, Igor; Gómez-Benito, Juana; Grendar, Marian; Grice, James W.; Guerrero-Gimenez, Martin E.; Gutiérrez, Andrés; Huedo-Medina, Tania B.; Jaffe, Klaus; Janyan, Armina; Karimnezhad, Ali; Korner-Nievergelt, Fränzi; Kosugi, Koji; Lachmair, Martin; Ledesma, Rubén D.; Limongi, Roberto; Liuzza, Marco T.; Lombardo, Rosaria; Marks, Michael J.; Meinlschmidt, Gunther; Nalborczyk, Ladislas; Nguyen, Hung T.; Ospina, Raydonal; Perezgonzalez, Jose D.; Pfister, Roland; Rahona, Juan J.; Rodríguez-Medina, David A.; Romão, Xavier; Ruiz-Fernández, Susana; Suarez, Isabel; Tegethoff, Marion; Tejo, Mauricio; van de Schoot, Rens; Vankov, Ivan I.; Velasco-Forero, Santiago; Wang, Tonghui; Yamada, Yuki; Zoppino, Felipe C. M.; Marmolejo-Ramos, Fernando

    2018-01-01

    We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable. PMID:29867666

  18. Null tDCS Effects in a Sustained Attention Task: The Modulating Role of Learning.

    PubMed

    Jacoby, Noa; Lavidor, Michal

    2018-01-01

    The purpose of this study was to investigate sustained attention through modulation of the fronto-cerebral network with transcranial direct current stimulation (tDCS) in adults with attention-deficit/hyperactivity disorder (ADHD) and control participants. Thirty-seven participants (21 with ADHD) underwent three separate sessions (baseline, active tDCS, and sham) and performed the MOXO Continuous Performance Test (CPT). We applied double anodal stimulation of 1.8 mA tDCS for 20 min over the left and right dorsolateral prefrontal cortex (DLPFC), with the cathode over the cerebellum. Baseline session revealed significant differences between ADHD and control participants in the MOXO-CPT attention and hyperactivity scores, validating the MOXO as a diagnostic tool. However, there were no tDCS effects in most MOXO-CPT measures, except hyperactivity, due to a significant learning effect. We conclude that learning and repetition effects in cognitive tasks need to be considered when designing within-subjects tDCS experiments, as there are natural improvements between sessions that conceal potential stimulation effects.

  19. No Clinically Significant Difference Between Adult and Pediatric IKDC Subjective Knee Evaluation Scores in Adults

    PubMed Central

    Stegmeier, Nicole; Oak, Sameer R.; O’Rourke, Colin; Strnad, Greg; Spindler, Kurt P.; Jones, Morgan; Farrow, Lutul D.; Andrish, Jack; Saluan, Paul

    2017-01-01

    Background: Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. Hypothesis: We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Study Design: Randomized crossover study design. Level of Evidence: Level 2. Methods: The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch’s 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. Results: A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R2 of 92.6%. Conclusion: There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Clinical Relevance: Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood. PMID

  20. 7. Exterior view of Components Test Laboratory (T27), looking south. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Exterior view of Components Test Laboratory (T-27), looking south. The wing in the immediate foreground houses the equipment room. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  1. Effectiveness comparison of partially executed t-way test suite based generated by existing strategies

    NASA Astrophysics Data System (ADS)

    Othman, Rozmie R.; Ahmad, Mohd Zamri Zahir; Ali, Mohd Shaiful Aziz Rashid; Zakaria, Hasneeza Liza; Rahman, Md. Mostafijur

    2015-05-01

    Consuming 40 to 50 percent of software development cost, software testing is one of the most resource consuming activities in software development lifecycle. To ensure an acceptable level of quality and reliability of a typical software product, it is desirable to test every possible combination of input data under various configurations. Due to combinatorial explosion problem, considering all exhaustive testing is practically impossible. Resource constraints, costing factors as well as strict time-to-market deadlines are amongst the main factors that inhibit such consideration. Earlier work suggests that sampling strategy (i.e. based on t-way parameter interaction or called as t-way testing) can be effective to reduce number of test cases without effecting the fault detection capability. However, for a very large system, even t-way strategy will produce a large test suite that need to be executed. In the end, only part of the planned test suite can be executed in order to meet the aforementioned constraints. Here, there is a need for test engineers to measure the effectiveness of partially executed test suite in order for them to assess the risk they have to take. Motivated by the abovementioned problem, this paper presents the effectiveness comparison of partially executed t-way test suite generated by existing strategies using tuples coverage method. Here, test engineers can predict the effectiveness of the testing process if only part of the original test cases is executed.

  2. Significant Artifact Reduction at 1.5T and 3T MRI by the Use of a Cochlear Implant with Removable Magnet: An Experimental Human Cadaver Study

    PubMed Central

    Wagner, Franca; Wimmer, Wilhelm; Leidolt, Lars; Vischer, Mattheus; Weder, Stefan; Wiest, Roland; Mantokoudis, Georgios; Caversaccio, Marco D.

    2015-01-01

    Objective Cochlear implants (CIs) are standard treatment for postlingually deafened individuals and prelingually deafened children. This human cadaver study evaluated diagnostic usefulness, image quality and artifacts in 1.5T and 3T magnetic resonance (MR) brain scans after CI with a removable magnet. Methods Three criteria (diagnostic usefulness, image quality, artifacts) were assessed at 1.5T and 3T in five cadaver heads with CI. The brain magnetic resonance scans were performed with and without the magnet in situ. The criteria were analyzed by two blinded neuroradiologists, with focus on image distortion and limitation of the diagnostic value of the acquired MR images. Results MR images with the magnet in situ were all compromised by artifacts caused by the CI. After removal of the magnet, MR scans showed an unequivocal artifact reduction with significant improvement of the image quality and diagnostic usefulness, both at 1.5T and 3T. Visibility of the brain stem, cerebellopontine angle, and parieto-occipital lobe ipsilateral to the CI increased significantly after magnet removal. Conclusions The results indicate the possible advantages for 1.5T and 3T MR scanning of the brain in CI carriers with removable magnets. Our findings support use of CIs with removable magnets, especially in patients with chronic intracranial pathologies. PMID:26200775

  3. Significant Artifact Reduction at 1.5T and 3T MRI by the Use of a Cochlear Implant with Removable Magnet: An Experimental Human Cadaver Study.

    PubMed

    Wagner, Franca; Wimmer, Wilhelm; Leidolt, Lars; Vischer, Mattheus; Weder, Stefan; Wiest, Roland; Mantokoudis, Georgios; Caversaccio, Marco D

    2015-01-01

    Cochlear implants (CIs) are standard treatment for postlingually deafened individuals and prelingually deafened children. This human cadaver study evaluated diagnostic usefulness, image quality and artifacts in 1.5T and 3T magnetic resonance (MR) brain scans after CI with a removable magnet. Three criteria (diagnostic usefulness, image quality, artifacts) were assessed at 1.5T and 3T in five cadaver heads with CI. The brain magnetic resonance scans were performed with and without the magnet in situ. The criteria were analyzed by two blinded neuroradiologists, with focus on image distortion and limitation of the diagnostic value of the acquired MR images. MR images with the magnet in situ were all compromised by artifacts caused by the CI. After removal of the magnet, MR scans showed an unequivocal artifact reduction with significant improvement of the image quality and diagnostic usefulness, both at 1.5T and 3T. Visibility of the brain stem, cerebellopontine angle, and parieto-occipital lobe ipsilateral to the CI increased significantly after magnet removal. The results indicate the possible advantages for 1.5T and 3T MR scanning of the brain in CI carriers with removable magnets. Our findings support use of CIs with removable magnets, especially in patients with chronic intracranial pathologies.

  4. Revealing Students' Cognitive Structure about Physical and Chemical Change: Use of a Word Association Test

    ERIC Educational Resources Information Center

    Yildirir, Hasene Esra; Demirkol, Hatice

    2018-01-01

    The current study aimed at examining the utility of a word association test in revealing students' cognitive structure in a specific chemistry topic through a word association test. The participants were 153 6th graders in a western Turkish city. The results revealed that the word association test serves a useful purpose in exploring the students'…

  5. Testing the Difference of Correlated Agreement Coefficients for Statistical Significance

    ERIC Educational Resources Information Center

    Gwet, Kilem L.

    2016-01-01

    This article addresses the problem of testing the difference between two correlated agreement coefficients for statistical significance. A number of authors have proposed methods for testing the difference between two correlated kappa coefficients, which require either the use of resampling methods or the use of advanced statistical modeling…

  6. 2. Exterior view of Components Test Laboratory (T27), looking southeast. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Exterior view of Components Test Laboratory (T-27), looking southeast. The building wing on the left houses the equipment room and that on the right houses Test Cell 8 (oxidizer) and the oxidizer storage pit or vault. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  7. 3. Exterior view of Components Test Laboratory (T27), looking southeast. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Exterior view of Components Test Laboratory (T-27), looking southeast. The building wing on the left houses the equipment room, and that on the right houses Test Cell 8 (oxidizer) and the oxidizer storage pit or vault. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  8. [Diagnostic significance of T2W hypointensity of the sella].

    PubMed

    Rousset, P; Cattin, F; Chiras, J; Bonneville, J F; Bonneville, F

    2009-06-01

    Normal anatomical structures and lesions characterized by low T2W signal intensity are reviewed in this pictorial essay. The purpose is to demonstrate how evaluation of the appearance, shape and exact anatomical location of the T2W hypointense sellar region structure, correlated with its T1W signal intensity, can based on the clinical context lead to an appropriate differential diagnosis.

  9. Concurrent tACS-fMRI Reveals Causal Influence of Power Synchronized Neural Activity on Resting State fMRI Connectivity.

    PubMed

    Bächinger, Marc; Zerbi, Valerio; Moisa, Marius; Polania, Rafael; Liu, Quanying; Mantini, Dante; Ruff, Christian; Wenderoth, Nicole

    2017-05-03

    Resting state fMRI (rs-fMRI) is commonly used to study the brain's intrinsic neural coupling, which reveals specific spatiotemporal patterns in the form of resting state networks (RSNs). It has been hypothesized that slow rs-fMRI oscillations (<0.1 Hz) are driven by underlying electrophysiological rhythms that typically occur at much faster timescales (>5 Hz); however, causal evidence for this relationship is currently lacking. Here we measured rs-fMRI in humans while applying transcranial alternating current stimulation (tACS) to entrain brain rhythms in left and right sensorimotor cortices. The two driving tACS signals were tailored to the individual's α rhythm (8-12 Hz) and fluctuated in amplitude according to a 1 Hz power envelope. We entrained the left versus right hemisphere in accordance to two different coupling modes where either α oscillations were synchronized between hemispheres (phase-synchronized tACS) or the slower oscillating power envelopes (power-synchronized tACS). Power-synchronized tACS significantly increased rs-fMRI connectivity within the stimulated RSN compared with phase-synchronized or no tACS. This effect outlasted the stimulation period and tended to be more effective in individuals who exhibited a naturally weak interhemispheric coupling. Using this novel approach, our data provide causal evidence that synchronized power fluctuations contribute to the formation of fMRI-based RSNs. Moreover, our findings demonstrate that the brain's intrinsic coupling at rest can be selectively modulated by choosing appropriate tACS signals, which could lead to new interventions for patients with altered rs-fMRI connectivity. SIGNIFICANCE STATEMENT Resting state fMRI (rs-fMRI) has become an important tool to estimate brain connectivity. However, relatively little is known about how slow hemodynamic oscillations measured with fMRI relate to electrophysiological processes. It was suggested that slowly fluctuating power envelopes of electrophysiological

  10. Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA-seq

    PubMed Central

    Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E.; He, Zhaoren; Aigner, Stefan; Metz, Patrick J.; Yu, Bingfei; Wehrens, Ellen J.; Lopez, Justine; Kim, Stephanie H.; Zuniga, Elina I.; Goldrath, Ananda W.; Chang, John T.; Yeo, Gene W.

    2017-01-01

    SUMMARY During microbial infection, responding CD8+ T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA sequencing approach and analyzed individual CD8+ T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants controlling CD8+ T lymphocyte fate specification. These findings suggest a model of terminal effector cell differentiation initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, highlighting the power and necessity of single-cell approaches. PMID:28218746

  11. Prognostic significance of inverse spatial QRS-T angle circadian pattern in myocardial infarction survivors.

    PubMed

    Giannopoulos, Georgios; Dilaveris, Polychronis; Batchvarov, Velislav; Synetos, Andreas; Hnatkova, Katerina; Gatzoulis, Konstantinos; Malik, Marek; Stefanadis, Christodoulos

    2009-01-01

    We investigated the predictive value of the spatial QRS-T angle (QRSTA) circadian variation in myocardial infarction (MI) patients. Analyzing 24-hour recordings (SEER MC, GE Marquette) from 151 MI patients (age 63 +/- 12.7), the QRSTA was computed in derived XYZ leads. QRS-T angle values were compared between daytime and night time. The end point was cardiac death or life-threatening ventricular arrhythmia in 1 year. Overall, QRSTA was slightly higher during the day vs. the night (91 degrees vs. 87 degrees, P = .005). However, 33.8% of the patients showed an inverse diurnal QRSTA variation (higher values at night), which was correlated to the outcome (P = .001, odds ratio 6.7). In multivariate analysis, after entering all factors exhibiting univariate trend towards significance, inverse QRSTA circadian pattern remained significant (P = .036). Inverse QRSTA circadian pattern was found to be associated with adverse outcome (22.4%) in MI patients, whereas a normal pattern was associated (96%) with a favorable outcome.

  12. Identification of significant features by the Global Mean Rank test.

    PubMed

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2014-01-01

    With the introduction of omics-technologies such as transcriptomics and proteomics, numerous methods for the reliable identification of significantly regulated features (genes, proteins, etc.) have been developed. Experimental practice requires these tests to successfully deal with conditions such as small numbers of replicates, missing values, non-normally distributed expression levels, and non-identical distributions of features. With the MeanRank test we aimed at developing a test that performs robustly under these conditions, while favorably scaling with the number of replicates. The test proposed here is a global one-sample location test, which is based on the mean ranks across replicates, and internally estimates and controls the false discovery rate. Furthermore, missing data is accounted for without the need of imputation. In extensive simulations comparing MeanRank to other frequently used methods, we found that it performs well with small and large numbers of replicates, feature dependent variance between replicates, and variable regulation across features on simulation data and a recent two-color microarray spike-in dataset. The tests were then used to identify significant changes in the phosphoproteomes of cancer cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two independently published mass spectrometry-based studies. MeanRank outperformed the other global rank-based methods applied in this study. Compared to the popular Significance Analysis of Microarrays and Linear Models for Microarray methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits more consistent behavior regarding the degree of regulation and is robust against the choice of preprocessing methods. MeanRank does not require any imputation of missing values, is easy to understand, and yields results that are easy to interpret. The software implementing the algorithm is freely available for academic and commercial use.

  13. NCHRP report 350 test 3-11 of the modified T8 bridge rail.

    DOT National Transportation Integrated Search

    2009-04-01

    A new flexible bridge rail system, referred to as the T8 rail, was designed as a replacement for the T6 rail in high-speed applications on culverts and thin deck structures. The T8 rail failed a crash test when the breakaway posts failed the thin dec...

  14. An association network analysis among microeukaryotes and bacterioplankton reveals algal bloom dynamics.

    PubMed

    Tan, Shangjin; Zhou, Jin; Zhu, Xiaoshan; Yu, Shichen; Zhan, Wugen; Wang, Bo; Cai, Zhonghua

    2015-02-01

    Algal blooms are a worldwide phenomenon and the biological interactions that underlie their regulation are only just beginning to be understood. It is established that algal microorganisms associate with many other ubiquitous, oceanic organisms, but the interactions that lead to the dynamics of bloom formation are currently unknown. To address this gap, we used network approaches to investigate the association patterns among microeukaryotes and bacterioplankton in response to a natural Scrippsiella trochoidea bloom. This is the first study to apply network approaches to bloom dynamics. To this end, terminal restriction fragment (T-RF) length polymorphism analysis showed dramatic changes in community compositions of microeukaryotes and bacterioplankton over the blooming period. A variance ratio test revealed significant positive overall associations both within and between microeukaryotic and bacterioplankton communities. An association network generated from significant correlations between T-RFs revealed that S. trochoidea had few connections to other microeukaryotes and bacterioplankton and was placed on the edge. This lack of connectivity allowed for the S. trochoidea sub-network to break off from the overall network. These results allowed us to propose a conceptual model for explaining how changes in microbial associations regulate the dynamics of an algal bloom. In addition, key T-RFs were screened by principal components analysis, correlation coefficients, and network analysis. Dominant T-RFs were then identified through 18S and 16S rRNA gene clone libraries. Results showed that microeukaryotes clustered predominantly with Dinophyceae and Perkinsea while the majority of bacterioplankton identified were Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. The ecologi-cal roles of both were discussed in the context of these findings. © 2014 Phycological Society of America.

  15. Evidence-based best practices for EGFR T790M testing in lung cancer in Canada.

    PubMed

    Stockley, T; Souza, C A; Cheema, P K; Melosky, B; Kamel-Reid, S; Tsao, M S; Spatz, A; Karsan, A

    2018-04-01

    Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as first-line systemic therapy for patients with non-small-cell lung cancer (nsclc) having mutations in the EGFR gene. Resistance to tkis eventually occurs in all nsclc patients treated with such drugs. In patients with resistance to tkis caused by the EGFR T790M mutation, the third-generation tki osimertinib is now the standard of care. For optimal patient management, accurate EGFR T790M testing is required. A multidisciplinary working group of pathologists, laboratory medicine specialists, medical oncologists, a respirologist, and a thoracic radiologist from across Canada was convened to discuss best practices for EGFR T790M mutation testing in Canada. The group made recommendations in the areas of the testing algorithm and the pre-analytic, analytic, and post-analytic aspects of clinical testing for both tissue testing and liquid biopsy circulating tumour dna testing. The recommendations aim to improve EGFR T790M testing in Canada and to thereby improve patient care.

  16. The Use of Time Series Analysis and t Tests with Serially Correlated Data Tests.

    ERIC Educational Resources Information Center

    Nicolich, Mark J.; Weinstein, Carol S.

    1981-01-01

    Results of three methods of analysis applied to simulated autocorrelated data sets with an intervention point (varying in autocorrelation degree, variance of error term, and magnitude of intervention effect) are compared and presented. The three methods are: t tests; maximum likelihood Box-Jenkins (ARIMA); and Bayesian Box Jenkins. (Author/AEF)

  17. No significant effect of transcranial direct current stimulation (tDCS) found on simple motor reaction time comparing 15 different simulation protocols.

    PubMed

    Horvath, Jared Cooney; Carter, Olivia; Forte, Jason D

    2016-10-01

    Research exploring the behavioral impact of transcranial direct current stimulation (tDCS) over M1 has produced homogenous results. The most common explanations to address this homogeneity concerns the differential impact of varied tDCS parameters (such as stimulation intensity or electrode montage). To explore this, we systematically examined the effects of 15 different tDCS protocols on a well-elucidated neurobehavioral system: simple visual motor reaction time (smRT). For the initial phase of this study, 150 healthy participants were randomly assigned to one of 5 experimental groups (2mA anodal, 2mA cathodal, 1mA anodal, 1mA cathodal, or sham) across 3 different conditions (orbitofrontal, bilateral, or extracephalic reference electrode location). The active electrode was always placed over M1 and tDCS lasted for 20min. Starting ~5min prior to stimulation and running continuously for ~30min, participants were repeatedly presented with a visual cue centered on a computer monitor and asked to press a response button as quickly as possible at stimulus onset (stimuli number: 100 pre-, 400 during-, and 100-post stimulation - interstimulus interval: 1-3s). Ex-gaussian distribution curves, miss, and error rates were determined for each normalized batch of 100 RTs and compared using a two-way ANOVA. As the largest group differences were seen with 2mA anodal (compared to sham) stimulation using an orbitofrontal montage, an additional 60 healthy participants were recruited to further test for significance in this condition. No significant impact of tDCS was seen on any parameter of smRT distribution, error rate, or miss rate, regardless of polarity, stimulation intensity, electrode montage, or stimulation-to-task relationship. Our results suggest that tDCS over M1 might not have a predictable or reliable effect on short duration smRT. Our results raise interesting questions regarding the mechanisms by which tDCS might modulate more complex motor behaviors. Additional

  18. Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths

    PubMed Central

    West, Janne; Blystad, Ida; Engström, Maria; Warntjes, Jan B. M.; Lundberg, Peter

    2013-01-01

    Background Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. Methods In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. Results Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001). Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. Conclusions Most of the brain was identically classified at the two field strengths, although some regional differences were observed. PMID:24066153

  19. T-cell immunity and cytokine production in cosmonauts after long-duration space flights

    NASA Astrophysics Data System (ADS)

    Morukov, B.; Rykova, M.; Antropova, E.; Berendeeva, T.; Ponomaryov, S.; Larina, I.

    2011-04-01

    Long-duration spaceflight effects on T-cell immunity and cytokine production were studied in 12 Russian cosmonauts flown onto the International Space Station. Specific assays were performed before launch and after landing and included analysis of peripheral leukocyte distribution, analysis of T-cell phenotype, expression of activation markers, apoptosis, proliferation of T cells in response to a mitogen, concentrations of cytokines in supernatants of cell cultures. Statistically significant increase was observed in leukocytes', lymphocytes', monocytes' and granulocytes' total number, increase in percentage and absolutely number of CD3 +CD4 +-cells, CD4 +CD45RA +-cells and CD4 +CD45RA +/CD4 +CD45RО + ratio, CD4 +CD25 +Bright regulatory cells ( p<0,05) in peripheral blood after landing. T-lymphocytes' capacity to present CD69 and CD25 on its own surfaces was increased for the majority of crewmembers. Analysis of T-cell response to PHA-stimulation in vitro revealed there were some trends toward reduced proliferation of stimulated T-lymphocytes. There was an apparent post flight decrease in secreted IFN-g for the majority of crewmembers and in most instances there was elevation in secreted IL-10. It revealed depression of IFN-g/IL-10 ratio after flight. Correlation analysis according to Spearman's rank correlation test established significant positive correlations ( p<0.05) between cytokine production and T-cell activation (CD25+, CD38+) and negative correlation ( p<0.05) between cytokine production and number of bulk memory CD4+T-cells (CD45RO+). Thus, these results suggest that T-cell dysfunction can be conditioned by cytokine dysbalance and could lead to development of disease after long-duration space flights.

  20. Multi-model Analysis of Diffusion-weighted Imaging of Normal Testes at 3.0 T: Preliminary Findings.

    PubMed

    Min, Xiangde; Feng, Zhaoyan; Wang, Liang; Cai, Jie; Li, Basen; Ke, Zan; Zhang, Peipei; You, Huijuan; Yan, Xu

    2018-04-01

    This study aimed to establish diffusion quantitative parameters (apparent diffusion coefficient [ADC], DDC, α, D app , and K app ) in normal testes at 3.0 T. Sixty-four healthy volunteers in two age groups (A: 10-39 years; B: ≥ 40 years) underwent diffusion-weighted imaging scanning at 3.0 T. ADC 1000 , ADC 2000 , ADC 3000 , DDC, α, D app , and K app were calculated using the mono-exponential, stretched-exponential, and kurtosis models. The correlations between parameters and the age were analyzed. The parameters were compared between the age groups and between the right and the left testes. The average ADC 1000 , ADC 2000 , ADC 3000 , DDC, α, D app , and K app values did not significantly differ between the right and the left testes (P > .05 for all). The following significant correlations were found: positive correlations between age and testicular ADC 1000 , ADC 2000 , ADC 3000 , DDC, and D app (r = 0.516, 0.518, 0.518, 0.521, and 0.516, respectively; P < .01 for all) and negative correlations between age and testicular α and K app (r = -0.363, -0.427, respectively; P < .01 for both). Compared to group B, in group A, ADC 1000 , ADC 2000 , ADC 3000 , DDC, and D app were significantly lower (P < .05 for all), but α and K app were significantly higher (P < .05 for both). Our study demonstrated the applicability of the testicular mono-exponential, stretched-exponential, and kurtosis models. Our results can help establish a baseline for the normal testicular parameters in these diffusion models. The contralateral normal testis can serve as a suitable reference for evaluating the abnormalities of the other side. The effect of age on these parameters requires further attention. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  1. Test-retest reliability of prefrontal transcranial Direct Current Stimulation (tDCS) effects on functional MRI connectivity in healthy subjects.

    PubMed

    Wörsching, Jana; Padberg, Frank; Helbich, Konstantin; Hasan, Alkomiet; Koch, Lena; Goerigk, Stephan; Stoecklein, Sophia; Ertl-Wagner, Birgit; Keeser, Daniel

    2017-07-15

    Transcranial Direct Current Stimulation (tDCS) of the prefrontal cortex (PFC) can be used for probing functional brain connectivity and meets general interest as novel therapeutic intervention in psychiatric and neurological disorders. Along with a more extensive use, it is important to understand the interplay between neural systems and stimulation protocols requiring basic methodological work. Here, we examined the test-retest (TRT) characteristics of tDCS-induced modulations in resting-state functional-connectivity MRI (RS fcMRI). Twenty healthy subjects received 20minutes of either active or sham tDCS of the dorsolateral PFC (2mA, anode over F3 and cathode over F4, international 10-20 system), preceded and ensued by a RS fcMRI (10minutes each). All subject underwent three tDCS sessions with one-week intervals in between. Effects of tDCS on RS fcMRI were determined at an individual as well as at a group level using both ROI-based and independent-component analyses (ICA). To evaluate the TRT reliability of individual active-tDCS and sham effects on RS fcMRI, voxel-wise intra-class correlation coefficients (ICC) of post-tDCS maps between testing sessions were calculated. For both approaches, results revealed low reliability of RS fcMRI after active tDCS (ICC (2,1) = -0.09 - 0.16). Reliability of RS fcMRI (baselines only) was low to moderate for ROI-derived (ICC (2,1) = 0.13 - 0.50) and low for ICA-derived connectivity (ICC (2,1) = 0.19 - 0.34). Thus, for ROI-based analyses, the distribution of voxel-wise ICC was shifted to lower TRT reliability after active, but not after sham tDCS, for which the distribution was similar to baseline. The intra-individual variation observed here resembles variability of tDCS effects in motor regions and may be one reason why in this study robust tDCS effects at a group level were missing. The data can be used for appropriately designing large scale studies investigating methodological issues such as sources of variability and

  2. Iopanoic acid-induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients.

    PubMed

    Ramos-Dias, J C; Lengyel, A M

    1999-10-01

    Thyroid hormones participate in GH synthesis and secretion, and an impaired GH response to many pharmacological stimuli, including GH releasing hormone (GHRH), has been found in thyrotoxicosis. Although the mechanisms involved in this process have not been fully elucidated, there is evidence that thyroid hormones could act at both hypothalamic and pituitary levels. There are no data in the literature about the effect of an acute reduction of circulating T3 levels on GH secretion in hyperthyroidism. The GH responsiveness to GHRH was therefore evaluated in a group of hyperthyroid patients during short-term treatment with iopanoic acid. Iopanoic acid is a compound that induces a rapid decrease in serum T3 levels, mainly by inhibition of peripheral conversion of T4 to T3. To the authors' knowledge, there is no evidence of a direct effect of iopanoic acid on GH secretion. Hyperthyroid patients were submitted to a GHRH test (100 microg, i.v.) before (day 0), and on days 4, 7 and 15 after oral treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (200 mg every 8 h). A group of normal control subjects was also submitted to a single GHRH test (100 microg, i.v.). Nine patients with thyrotoxicosis (eight women, one man), with a mean age of 34 years, were studied. All patients had high serum levels of total T3 and total T4, and suppressed TSH levels. None of them had taken any medication for at least 3 months before the study. The patients were compared with a group of nine control subjects (five women, four men) with a mean age of 31 years. GH and TSH were measured by immunofluorometric assays. Total T3, total T4 and IGF-I were determined by radioimmunoassay. Albumin levels were measured by a colorimetric method. Iopanoic acid induced a rapid and maintained decrease in serum T3 concentrations, with a significant reduction on days 4, 7 and 15 compared with pre-treatment values. In hyperthyroidism, peak GH levels (mean +/- SE mU/l) after GHRH were significantly

  3. Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages.

    PubMed

    Machkovech, Heather M; Bedford, Trevor; Suchard, Marc A; Bloom, Jesse D

    2015-11-01

    Numerous experimental studies have demonstrated that CD8(+) T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8(+) T cells. Here we use a novel computational approach to test for selection in CD8(+) T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8(+) T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8(+) T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8(+) T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8(+) T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal

  4. Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

    PubMed Central

    Machkovech, Heather M.; Bedford, Trevor; Suchard, Marc A.

    2015-01-01

    ABSTRACT Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. IMPORTANCE There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+ T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal

  5. Use of "t"-Test and ANOVA in Career-Technical Education Research

    ERIC Educational Resources Information Center

    Rojewski, Jay W.; Lee, In Heok; Gemici, Sinan

    2012-01-01

    Use of t-tests and analysis of variance (ANOVA) procedures in published research from three scholarly journals in career and technical education (CTE) during a recent 5-year period was examined. Information on post hoc analyses, reporting of effect size, alpha adjustments to account for multiple tests, power, and examination of assumptions…

  6. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lowden, Michael J.; Skorupski, Karen; Pellegrini, Maria

    2010-03-04

    Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 {angstrom} resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding thatmore » cis-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.« less

  7. Small Scale Trace Contaminant Testing of SA9T at Ambient and Reduced Pressure Conditions

    NASA Technical Reports Server (NTRS)

    Broerman, Craig; Sweterlitsch, Jeffrey

    2011-01-01

    A principle concern for air revitalization technology in a closed loop system is the capability to control carbon dioxide (CO2) and humidity (H2O). An amine based sorbent technology, SA9T, has long been evaluated for use in this application and several programs are evaluating it for use in both a cabin as well as space suit applications. While the CO2 and H2O performance of the sorbent has been tested extensively, the question of how trace contaminants impact performance requires further evaluation. This paper presents experimental results of small scale SA9T testing that was performed over a variety of test conditions and with a variety of trace contaminants. Testing evaluated the ability of SA9T media to sufficiently remove CO2 and H2O after exposure to a fully saturated trace contaminant at ambient conditions. Testing also evaluated the impact of CO2 and H2O removal performance at suit loop pressures during cyclic operation with a constant inlet contaminant load. In addition, testing evaluated the performance of SA9T at ambient conditions in a continuous 30-day test with a mixed trace contaminant stream.

  8. TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia

    PubMed Central

    Catakovic, Kemal; Gassner, Franz Josef; Ratswohl, Christoph; Zaborsky, Nadja; Rebhandl, Stefan; Schubert, Maria; Steiner, Markus; Gutjahr, Julia Christine; Pleyer, Lisa; Egle, Alexander; Hartmann, Tanja Nicole; Greil, Richard; Geisberger, Roland

    2018-01-01

    ABSTRACT While research on T cell exhaustion in context of cancer particularly focuses on CD8+ cytotoxic T cells, the role of inhibitory receptors on CD4+ T-helper cells have remained largely unexplored. TIGIT is a recently identified inhibitory receptor on T cells and natural killer (NK) cells. In this study, we examined TIGIT expression on T cell subsets from CLL patients. While we did not observe any differences in TIGIT expression in CD8+ T cells of healthy controls and CLL cells, we found an enrichment of TIGIT+ T cells in the CD4+ T cell compartment in CLL. Intriguingly, CLL patients with an advanced disease stage displayed elevated numbers of CD4+ TIGIT+ T cells compared to low risk patients. Autologous CLL-T cell co-culture assays revealed that depleting CD4+ TIGIT+ expressing T cells from co-cultures significantly decreased CLL viability. Accordingly, a supportive effect of TIGIT+CD4+ T cells on CLL cells in vitro could be recapitulated by blocking the interaction of TIGIT with its ligands using TIGIT-Fc molecules, which also impeded the T cell specific production of CLL-prosurvival cytokines. Our data reveal that TIGIT+CD4+T cells provide a supportive microenvironment for CLL cells, representing a potential therapeutic target for CLL treatment. PMID:29296521

  9. Patterns of Statewide Test Participation for Students with Significant Cognitive Disabilities

    ERIC Educational Resources Information Center

    Saven, Jessica L.; Anderson, Daniel; Nese, Joseph F. T.; Farley, Dan; Tindal, Gerald

    2016-01-01

    Students with significant cognitive disabilities are eligible to participate in two statewide testing options for accountability: alternate assessments or general assessments with appropriate accommodations. Participation guidelines are generally quite vague, leading to students "switching" test participation between years. In this…

  10. Testing Viable f(T) Models with Current Observations

    NASA Astrophysics Data System (ADS)

    Xu, Bing; Yu, Hongwei; Wu, Puxun

    2018-03-01

    We perform observational tests on the f(T) gravity with the BAO data (including the BOSS DR 12 galaxy sample, the DR12 Lyα-Forests measurement, the new eBOSS DR14 quasar sample, the 6dFGS, and the SDSS), the CMB distance priors from the Planck 2015, the SNIa data from the joint light-curve analysis, the latest H(z) data, and the local value of the Hubble constant. Six different f(T) models are investigated. Furthermore, the ΛCDM is also considered. All models are compared by using the Akaike information criteria (AIC) and the Bayesian information criteria (BIC). Our results show that the ΛCDM remains to be the most favored model by current observations. However, there are also the Hubble constant tension between the Planck measurements and the local Universe observations and the tension between the CMB data and the H(z) data in the ΛCDM. For f(T) models considered in this paper, half, which can reduce to the ΛCDM, have values of {{χ }2}\\min smaller than that of the ΛCDM and can relieve the tensions existing in the ΛCDM. However, they are punished slightly by the BIC due to one extra parameter. Two of six f(T) models, in which the crossing of the phantom divide line can be realized for the equation of state of the effective dark energy and this crossing is shown in this paper to be favored by current observations, are punished by the information criteria. In addition, we find that the logarithmic f(T) model is excluded by cosmological observations.

  11. Null tDCS Effects in a Sustained Attention Task: The Modulating Role of Learning

    PubMed Central

    Jacoby, Noa; Lavidor, Michal

    2018-01-01

    The purpose of this study was to investigate sustained attention through modulation of the fronto-cerebral network with transcranial direct current stimulation (tDCS) in adults with attention-deficit/hyperactivity disorder (ADHD) and control participants. Thirty-seven participants (21 with ADHD) underwent three separate sessions (baseline, active tDCS, and sham) and performed the MOXO Continuous Performance Test (CPT). We applied double anodal stimulation of 1.8 mA tDCS for 20 min over the left and right dorsolateral prefrontal cortex (DLPFC), with the cathode over the cerebellum. Baseline session revealed significant differences between ADHD and control participants in the MOXO-CPT attention and hyperactivity scores, validating the MOXO as a diagnostic tool. However, there were no tDCS effects in most MOXO-CPT measures, except hyperactivity, due to a significant learning effect. We conclude that learning and repetition effects in cognitive tasks need to be considered when designing within-subjects tDCS experiments, as there are natural improvements between sessions that conceal potential stimulation effects. PMID:29681876

  12. Suitability of hair type for dermatophytes perforation and differential diagnosis of T. mentagrophytes from T. verrucosum.

    PubMed

    Al-Janabi, Ali Abdul Hussein S; Ai-Tememi, Nabaa N; Ai-Shammari, Rabab A; Ai-Assadi, Abdul Hadi A

    2016-04-01

    Most of the dermatophyte species have the ability to perforate hair structure and consume its contents of keratin through secretion of keratinase enzyme. Two clinical isolated species of dermatophytes were diagnosed as Trichophyton mentagrophytes var. granulosum and Trichophyton verrucosum. To determine the perforation ability, the isolated fungi were incubated with the hair of four different animals (rabbit, rat, cow and cat) and human hairs with three different colours (black, albino and bleached yellow) for different periods. Variable perforating ability of T. mentagrophytes was shown in rat hair and all types of human hair after 15 days, while other mammalian hairs exhibited resistance to this fungal activity. On the other hand, T. verrucosum was revealed a slow perforating ability, which needed a long time (60 days) for most of tested hairs. Perforation of human black hair could be considered a diagnostic test for differentiation between T. mentagrophytes and T. verrucosum. In conclusion, the treated or untreated human hair was considered more suitable to use as a source of keratin for the growth of dermatophytes than animal hairs. The human black hair was a best type of hair to use in the perforating test for differentiation between T. mentagrophytes and T. verrucosum. © 2016 Blackwell Verlag GmbH.

  13. Test of 4-body Theory via Polarized p-T Capture Below 80 keV

    NASA Astrophysics Data System (ADS)

    Canon, R. S.; Gaff, S. J.; Kelley, J. H.; Schreiber, E. C.; Weller, H. R.; Wulf, E. A.; Prior, R. M.; Spraker, M.; Tilley, D. R.

    1998-10-01

    Our previous study of polarized p-d capture at energies below 80 keV revealed the major role played by MEC effects and provided a clean testing ground for state-of-the-art 3-body theory (the ``Ay puzzle'' remains)(G. Schmid et al); PRL 76, 3088(1996); PRC 56, 2565(1997). Four-body theory is on the threshold(A. Fonseca,W. Glöckle,A. Kievsky,H. Witala;Private communication) of being able to make similar ab-initio predictions. The p-T capture reaction is expected to exhibit strong MEC effects at very low energies for reasons similar to those in p-d capture. Preliminary results indicate finite values of A_y(90^circ) in the 50-80 keV region. These results will be discussed with respect to their implications on the M1 strength present in this reaction. Plans for future measurements and analysis will also be described.

  14. Shaping Up the Practice of Null Hypothesis Significance Testing.

    ERIC Educational Resources Information Center

    Wainer, Howard; Robinson, Daniel H.

    2003-01-01

    Discusses criticisms of null hypothesis significance testing (NHST), suggesting that historical use of NHST was reasonable, and current users should read Sir Ronald Fisher's applied work. Notes that modifications to NHST and interpretations of its outcomes might better suit the needs of modern science. Concludes that NHST is most often useful as…

  15. A Report on the Present Status of Engineering Mathematics Test (EMaT)

    NASA Astrophysics Data System (ADS)

    Watanabe, Toshimasa; Takafuji, Daisuke

    The aim of Engineering Mathematics Test (EMaT) is to make sure what essentials in curriculum of Engineering Mathematics is, and to assess university students’ core academic competence and achievement of Engineering Mathematics, helping assurance of students’ academic ability. It is useful for professors to evaluate teaching effect of the classes, and this evaluation would help them improve curricula. Scores can be available for both graduate school entrance examinations and employment tests, leading to selecting persons with basic academic ability in Engineering Mathematics. The scope includes fundamentals in Calculus, Linear Algebra, Differential Equations, and Probability and Statistics. It is open to all students free of charge, and is annually given once in December. In 2007, 2,396 students from 35 universities took EMaT, and the total number of students who have taken EMaT in these 5 years is 6,240.

  16. Significance of acceleration period in a dynamic strength testing study.

    PubMed

    Chen, W L; Su, F C; Chou, Y L

    1994-06-01

    The acceleration period that occurs during isokinetic tests may provide valuable information regarding neuromuscular readiness to produce maximal contraction. The purpose of this study was to collect the normative data of acceleration time during isokinetic knee testing, to calculate the acceleration work (Wacc), and to determine the errors (ERexp, ERwork, ERpower) due to ignoring Wacc during explosiveness, total work, and average power measurements. Seven male and 13 female subjects attended the test by using the Cybex 325 system and electronic stroboscope machine for 10 testing speeds (30-300 degrees/sec). A three-way ANOVA was used to assess gender, direction, and speed factors on acceleration time, Wacc, and errors. The results indicated that acceleration time was significantly affected by speed and direction; Wacc and ERexp by speed, direction, and gender; and ERwork and ERpower by speed and gender. The errors appeared to increase when testing the female subjects, during the knee flexion test, or when speed increased. To increase validity in clinical testing, it is important to consider the acceleration phase effect, especially in higher velocity isokinetic testing or for weaker muscle groups.

  17. Phylogeographic analysis reveals significant spatial genetic structure of Incarvillea sinensis as a product of mountain building.

    PubMed

    Chen, Shaotian; Xing, Yaowu; Su, Tao; Zhou, Zhekun; Dilcher, Emeritus David L; Soltis, Douglas E

    2012-04-30

    Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM) in 705 individuals from 47 localities. A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P < 0.05). The survey detected two highly divergent cpDNA lineages connected by a deep gap with allopatric distributions: the southern lineage with higher genetic diversity and differentiation in the eastern Qinghai-Tibet Plateau, and the northern lineage in the region outside the Qinghai-Tibet Plateau. The divergence between these two lineages was estimated at 4.4 MYA. A correlation between the genetic and the geographic distances indicates that genetic drift was more influential than gene flow in the northern clade with lower diversity and divergence. However, a scenario of regional equilibrium between gene flow and drift was shown for the southern clade. The feature of spatial distribution of the genetic diversity of the southern lineage possibly indicated that allopatric fragmentation was dominant in the collections from the eastern Qinghai-Tibet Plateau. The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and postglacial recolonization. Our

  18. Bench-Scale Trace Contaminant Testing of SA9T at Ambient and Reduced Pressure Conditions

    NASA Technical Reports Server (NTRS)

    Broerman, Craig; Sweterlitsch, Jeff

    2011-01-01

    A principal concern for air revitalization technology in a closed loop system is the capability to control carbon dioxide (CO2) and humidity (H2O). An amine based sorbent technology, SA9T, has been evaluated for use in this application and several programs are evaluating it for use in both cabin and space suit applications. While the CO2 and H2O performance of the sorbent has been tested extensively, the question of how trace contaminants impact performance requires further evaluation. This paper presents experimental results of bench-scale SA9T testing that was performed under a variety of test conditions and with several different trace contaminants. Tests were conducted to determine if the capacity of the SA9T media to sufficiently remove CO2 and H2O is compromised after exposure to a fully saturated trace contaminant at ambient conditions. Tests also were conducted to evaluate the performance of SA9T at ambient conditions in a continuous 30-day test with a mixed trace contaminant stream. In addition, testing also evaluated the impact of CO2 and H2O removal performance at suit loop pressures (29.6 KPa/4.3 psia) during cyclic operation with a constant inlet contaminant load.

  19. Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis.

    PubMed

    Savas, Peter; Virassamy, Balaji; Ye, Chengzhong; Salim, Agus; Mintoff, Christopher P; Caramia, Franco; Salgado, Roberto; Byrne, David J; Teo, Zhi L; Dushyanthen, Sathana; Byrne, Ann; Wein, Lironne; Luen, Stephen J; Poliness, Catherine; Nightingale, Sophie S; Skandarajah, Anita S; Gyorki, David E; Thornton, Chantel M; Beavis, Paul A; Fox, Stephen B; Darcy, Phillip K; Speed, Terence P; Mackay, Laura K; Neeson, Paul J; Loi, Sherene

    2018-06-25

    The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival, particularly in triple-negative and HER2-overexpressing BC subtypes 1 . Although T cells are the predominant TIL population 2 , the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6,311 T cells isolated from human BCs and show that significant heterogeneity exists in the infiltrating T cell population. We demonstrate that BCs with a high number of TILs contained CD8 + T cells with features of tissue-resident memory T (T RM ) cell differentiation and that these CD8 + T RM cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8 + T RM gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple-negative breast cancer (TNBC) and provided better prognostication than CD8 expression alone. Our data suggest that CD8 + T RM cells contribute to BC immunosurveillance and are the key targets of modulation by immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of T RM cells will be crucial for successful immunotherapeutic development in BC.

  20. Advances in Testing the Statistical Significance of Mediation Effects

    ERIC Educational Resources Information Center

    Mallinckrodt, Brent; Abraham, W. Todd; Wei, Meifen; Russell, Daniel W.

    2006-01-01

    P. A. Frazier, A. P. Tix, and K. E. Barron (2004) highlighted a normal theory method popularized by R. M. Baron and D. A. Kenny (1986) for testing the statistical significance of indirect effects (i.e., mediator variables) in multiple regression contexts. However, simulation studies suggest that this method lacks statistical power relative to some…

  1. The I Don't Know Option in the Vocabulary Size Test

    ERIC Educational Resources Information Center

    Zhang, Xian

    2013-01-01

    The current study evaluates guessing behaviors in a vocabulary size test (VST) and examines whether including an "I don't know" in a VST may have an impact on the results of the test. One-hundred-fifty first-year students at a university in China took part in the study. They were randomly assigned to three groups. Each group took a…

  2. Laboratory simulation reveals significant impacts of ocean acidification on microbial community composition and host-pathogen interactions between the blood clam and Vibrio harveyi.

    PubMed

    Zha, Shanjie; Liu, Saixi; Su, Wenhao; Shi, Wei; Xiao, Guoqiang; Yan, Maocang; Liu, Guangxu

    2017-12-01

    It has been suggested that climate change may promote the outbreaks of diseases in the sea through altering the host susceptibility, the pathogen virulence, and the host-pathogen interaction. However, the impacts of ocean acidification (OA) on the pathogen components of bacterial community and the host-pathogen interaction of marine bivalves are still poorly understood. Therefore, 16S rRNA high-throughput sequencing and host-pathogen interaction analysis between blood clam (Tegillarca granosa) and Vibrio harveyi were conducted in the present study to gain a better understanding of the ecological impacts of ocean acidification. The results obtained revealed a significant impact of ocean acidification on the composition of microbial community at laboratory scale. Notably, the abundance of Vibrio, a major group of pathogens to many marine organisms, was significantly increased under ocean acidification condition. In addition, the survival rate and haemolytic activity of V. harveyi were significantly higher in the presence of haemolymph of OA treated T. granosa, indicating a compromised immunity of the clam and enhanced virulence of V. harveyi under future ocean acidification scenarios. Conclusively, the results obtained in this study suggest that future ocean acidification may increase the risk of Vibrio pathogen infection for marine bivalve species, such as blood clams. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

    PubMed

    D'Arcy, R; McDonnell, M; Spence, K; Courtney, C H

    2017-01-01

    A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T 4 ). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T 3 ) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging ( 123 I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T 3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. Free tri-iodothyronine (T 3 ) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T 4 ) or T 3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

  4. Performance and blood monitoring in sports: the artificial intelligence evoking target testing in antidoping (AR.I.E.T.T.A.) project.

    PubMed

    Manfredini, A F; Malagoni, A M; Litmanen, H; Zhukovskaja, L; Jeannier, P; Dal Follo, D; Felisatti, M; Besseberg, A; Geistlinger, M; Bayer, P; Carrabre, J E

    2011-03-01

    Substances and methods used to increase oxygen blood transport and physical performance can be detected in the blood, but the screening of the athletes to be tested remains a critical issue for the International Federations. This project, AR.I.E.T.T.A., aimed to develop a software capable of analysing athletes' hematological and performance profiles to detect abnormal patterns. One-hundred eighty athletes belonging to the International Biathlon Union gave written informed consent to have their hematological data, previously collected according to anti-doping rules, used to develop the AR.I.E.T.T.A. software. Software was developed with the included sections: 1) log-in; 2) data-entry: where data are loaded, stored and grouped; 3) analysis: where data are analysed, validated scores are calculated, and parameters are simultaneously displayed as statistics, tables and graphs, and individual or subpopulation profiles; 4) screening: where an immediate evaluation of the risk score of the present sample and/or the athlete under study is obtained. The sample risk score or AR.I.E.T.T.A. score is calculated by a simple computational system combining different parameters (absolute values and intra-individual variations) considered concurrently. The AR.I.E.T.T.A. score is obtained by the sum of the deviation units derived from each parameter, considering the shift of the present value from the reference values, based on the number of standard deviations. AR.I.E.T.T.A. enables a quick evaluation of blood results assisting surveillance programs and perform timely target testing controls on athletes by the International Federations. Future studies aiming to validate the AR.I.E.T.T.A. score and improve the diagnostic accuracy will improve the system.

  5. The Case for Use of Simple Difference Scores to Test the Significance of Differences in Mean Rates of Change in Controlled Repeated Measurements Designs

    ERIC Educational Resources Information Center

    Overall, John E.; Tonidandel, Scott

    2010-01-01

    A previous Monte Carlo study examined the relative powers of several simple and more complex procedures for testing the significance of difference in mean rates of change in a controlled, longitudinal, treatment evaluation study. Results revealed that the relative powers depended on the correlation structure of the simulated repeated measurements.…

  6. Experimental manipulation reveals a trade-off between weapons and testes.

    PubMed

    Somjee, U; Miller, C W; Tatarnic, N J; Simmons, L W

    2018-01-01

    Theory predicts a trade-off between sexually selected weapons used to secure mates and post-copulatory traits used to maximize fertilization success. However, individuals that have a greater capacity to acquire resources from the environment may invest more in both pre- and post-copulatory traits, and trade-offs may not be readily apparent. Here, we manipulate the phenotype of developing individuals to examine allocation trade-offs between weapons and testes in Mictis profana (Hemiptera: Coreidae), a species where the hind legs are sexually selected weapons used in contests over access to females. We experimentally prevented males from developing weapons by inducing them to autotomize their hind legs before the final moult to adulthood. We compared trait expression in this group to males where autotomy was induced in the mid-legs, which are presumably not under sexual selection to the same extent. We found males without weapons invested proportionally more in testes mass than those with their mid-legs removed. Males that developed to adulthood without weapons did not differ from the mid-leg removal group in other traits potentially under precopulatory sexual selection, other post-copulatory traits or naturally selected traits. In addition, a sample of adult males from the same population in the wild revealed a positive correlation between investment in testes and weapons. Our study presents a critical contribution to a growing body of literature suggesting the allocation of resources to pre- and post-copulatory sexual traits is influenced by a resource allocation trade-off and that this trade-off may only be revealed with experimental manipulation. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  7. Clinical radiobiology of stage T2-T3 bladder cancer.

    PubMed

    Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

    2004-09-01

    To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which

  8. Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles.

    PubMed Central

    Nisini, R; Paroli, M; Accapezzato, D; Bonino, F; Rosina, F; Santantonio, T; Sallusto, F; Amoroso, A; Houghton, M; Barnaba, V

    1997-01-01

    The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay

  9. Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells

    PubMed Central

    Cao, Lulu; Ding, Yiyuan; Hung, Norris; Yu, Kebing; Ritz, Anna; Raphael, Benjamin J.; Salomon, Arthur R.

    2012-01-01

    The SH2-domain-containing leukocyte protein of 76 kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCR signaling has been widely studied using the Jurkat human leukaemic T cell line through protein disruption or site-directed mutagenesis. However, a wide-scale characterization of SLP-76-dependant phosphorylation events is still lacking. Quantitative profiling of over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASP while reconfirming previously established regulation of Itk, PLCγ, and Erk phosphorylation by SLP-76. The absence of SLP-76 also perturbed the phosphorylation of Src family kinases (SFKs) Lck and Fyn, and subsequently a large number of SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway. PMID:23071622

  10. Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.

    PubMed

    Cao, Lulu; Ding, Yiyuan; Hung, Norris; Yu, Kebing; Ritz, Anna; Raphael, Benjamin J; Salomon, Arthur R

    2012-01-01

    The SH2-domain-containing leukocyte protein of 76 kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCR signaling has been widely studied using the Jurkat human leukaemic T cell line through protein disruption or site-directed mutagenesis. However, a wide-scale characterization of SLP-76-dependant phosphorylation events is still lacking. Quantitative profiling of over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASP while reconfirming previously established regulation of Itk, PLCγ, and Erk phosphorylation by SLP-76. The absence of SLP-76 also perturbed the phosphorylation of Src family kinases (SFKs) Lck and Fyn, and subsequently a large number of SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway.

  11. Statistical Significance Testing in Second Language Research: Basic Problems and Suggestions for Reform

    ERIC Educational Resources Information Center

    Norris, John M.

    2015-01-01

    Traditions of statistical significance testing in second language (L2) quantitative research are strongly entrenched in how researchers design studies, select analyses, and interpret results. However, statistical significance tests using "p" values are commonly misinterpreted by researchers, reviewers, readers, and others, leading to…

  12. Revealing barriers and facilitators to use a new genetic test: comparison of three user involvement methods.

    PubMed

    Rhebergen, Martijn D F; Visser, Maaike J; Verberk, Maarten M; Lenderink, Annet F; van Dijk, Frank J H; Kezic, Sanja; Hulshof, Carel T J

    2012-10-01

    We compared three common user involvement methods in revealing barriers and facilitators from intended users that might influence their use of a new genetic test. The study was part of the development of a new genetic test on the susceptibility to hand eczema for nurses. Eighty student nurses participated in five focus groups (n = 33), 15 interviews (n = 15) or questionnaires (n = 32). For each method, data were collected until saturation. We compared the mean number of items and relevant remarks that could influence the use of the genetic test obtained per method, divided by the number of participants in that method. Thematic content analysis was performed using MAXQDA software. The focus groups revealed 30 unique items compared to 29 in the interviews and 21 in the questionnaires. The interviews produced more items and relevant remarks per participant (1.9 and 8.4 pp) than focus groups (0.9 and 4.8 pp) or questionnaires (0.7 and 2.3 pp). All three involvement methods revealed relevant barriers and facilitators to use a new genetic test. Focus groups and interviews revealed substantially more items than questionnaires. Furthermore, this study suggests a preference for the use of interviews because the number of items per participant was higher than for focus groups and questionnaires. This conclusion may be valid for other genetic tests as well.

  13. Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal t6A tRNA modification.

    PubMed

    Pichard-Kostuch, Adeline; Zhang, Wenhua; Liger, Dominique; Daugeron, Marie-Claire; Letoquart, Juliette; Li de la Sierra-Gallay, Ines; Forterre, Patrick; Collinet, Bruno; van Tilbeurgh, Herman; Basta, Tamara

    2018-04-12

    N6-threonyl-carbamoyl adenosine (t6A) is a universal tRNA modification found at position 37, next to the anticodon, in almost all tRNAs decoding ANN codons (where N = A, U, G or C). t6A stabilizes the codon-anticodon interaction and hence promotes translation fidelity. The first step of the biosynthesis of t6A, the production of threonyl-carbamoyl adenylate (TC-AMP), is catalyzed by the Sua5/TsaC family of enzymes. While TsaC is a single domain protein, Sua5 enzymes are composed of the TsaC-like domain, a linker and an extra domain called SUA5 of unknown function. In the present study, we report structure-function analysis of Pyrococcus abyssi Sua5 (Pa-Sua5). Crystallographic data revealed binding sites for bicarbonate substrate and pyrophosphate product. The linker of Pa-Sua5 forms a loop structure that folds into the active site gorge and closes it. Using structure-guided mutational analysis we established that the conserved sequence motifs in the linker and the domain-domain interface are essential for the function of Pa-Sua5. We propose that the linker participates actively in the biosynthesis of TC-AMP by binding to ATP/PPi and by stabilizing the N-carboxy-L-threonine intermediate. Hence, TsaC orthologs which lack such a linker and SUA5 domain use different mechanism for TC-AMP synthesis. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  14. Preoperative detection of malignant liver tumors: Comparison of 3D-T2-weighted sequences with T2-weighted turbo spin-echo and single shot T2 at 1.5 T.

    PubMed

    Barat, Maxime; Soyer, Philippe; Dautry, Raphael; Pocard, Marc; Lo-Dico, Rea; Najah, Haythem; Eveno, Clarisse; Cassinotto, Christophe; Dohan, Anthony

    2018-03-01

    To assess the performances of three-dimensional (3D)-T2-weighted sequences compared to standard T2-weighted turbo spin echo (T2-TSE), T2-half-Fourier acquisition single-shot turbo spin-echo (T2-HASTE), diffusion weighted imaging (DWI) and 3D-T1-weighted VIBE sequences in the preoperative detection of malignant liver tumors. From 2012 to 2015, all patients of our institution undergoing magnetic resonance imaging (MRI) examination for suspected malignant liver tumors were prospectively included. Patients had contrast-enhanced 3D-T1-weighted, DWI, 3D-T2-SPACE, T2-HASTE and T2-TSE sequences. Imaging findings were compared with those obtained at follow-up, surgery and histopathological analysis. Sensitivities for the detection of malignant liver tumors were compared for each sequence using McNemar test. A subgroup analysis was conducted for HCCs. Image artifacts were analyzed and compared using Wilcoxon paired signed rank-test. Thirty-three patients were included: 13 patients had 40 hepatocellular carcinomas (HCC) and 20 had 54 liver metastases. 3D-T2-weighted sequences had a higher sensitivity than T2-weighted TSE sequences for the detection of malignant liver tumors (79.8% versus 68.1%; P < 0.001). The difference did not reach significance for HCC. T1-weighted VIBE and DWI had a higher sensitivity than T2-weighted sequences. 3D-T2-weighted-SPACE sequences showed significantly less artifacts than T2-weitghted TSE. 3D-T2-weighted sequences show very promising performances for the detection of liver malignant tumors compared to T2-weighted TSE sequences. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Testing Mediation in Structural Equation Modeling: The Effectiveness of the Test of Joint Significance

    ERIC Educational Resources Information Center

    Leth-Steensen, Craig; Gallitto, Elena

    2016-01-01

    A large number of approaches have been proposed for estimating and testing the significance of indirect effects in mediation models. In this study, four sets of Monte Carlo simulations involving full latent variable structural equation models were run in order to contrast the effectiveness of the currently popular bias-corrected bootstrapping…

  16. 1. Exterior view of Components Test Laboratory (T27), looking southeast ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Exterior view of Components Test Laboratory (T-27), looking southeast from hill north of structure. The building wing in the right foreground houses Test Cell 8 (oxidizer) and the oxidizer storage pit or vault. Test Cell 10 is located in the center background, Test Cell 9 is at the far left, and the equipment room is in the immediate left foreground. The control room is in the center of the structure and abuts the aforementioned test cell and equipment room wings. This structure served as a facility for testing, handling, and storage of Titan II's hydrazine- and nitrogen teteroxide-based propellant system components for compatability determinations. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  17. Novel ventilation design of combining spacer and mesh structure in sports T-shirt significantly improves thermal comfort.

    PubMed

    Sun, Chao; Au, Joe Sau-chuen; Fan, Jintu; Zheng, Rong

    2015-05-01

    This paper reports on novel ventilation design in sports T-shirt, which combines spacer and mesh structure, and experimental evidence on the advantages of design in improving thermal comfort. Evaporative resistance (Re) and thermal insulation (Rc) of T-shirts were measured using a sweating thermal manikin under three different air velocities. Moisture permeability index (i(m)) was calculated to compare the different designed T-shirts. The T-shirts of new and conventional designs were also compared by wearer trials, which were comprised of 30 min treadmill running followed by 10 min rest. Skin temperature, skin relative humidity, heart rate, oxygen inhalation and energy expenditure were monitored, and subjective sensations were asked. Results demonstrated that novel T-shirt has 11.1% significant lower im than control sample under windy condition. The novel T-shirt contributes to reduce the variation of skin temperature and relative humidity up to 37% and 32%, as well as decrease 3.3% energy consumption during exercise. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  18. Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients.

    PubMed

    Castro-Sesquen, Yagahira E; Gilman, Robert H; Mejia, Carolina; Clark, Daniel E; Choi, Jeong; Reimer-McAtee, Melissa J; Castro, Rosario; Valencia-Ayala, Edward; Flores, Jorge; Bowman, Natalie; Castillo-Neyra, Ricardo; Torrico, Faustino; Liotta, Lance; Bern, Caryn; Luchini, Alessandra

    2016-02-01

    Early diagnosis of reactivated Chagas disease in HIV patients could be lifesaving. In Latin America, the diagnosis is made by microscopical detection of the T. cruzi parasite in the blood; a diagnostic test that lacks sensitivity. This study evaluates if levels of T. cruzi antigens in urine, determined by Chunap (Chagas urine nanoparticle test), are correlated with parasitemia levels in T. cruzi/HIV co-infected patients. T. cruzi antigens in urine of HIV patients (N = 55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. Reactivation of Chagas disease was defined by the observation of parasites in blood by microscopy. Parasitemia levels in patients with serology positive for Chagas disease were classified as follows: High parasitemia or reactivation of Chagas disease (detectable parasitemia by microscopy), moderate parasitemia (undetectable by microscopy but detectable by qPCR), and negative parasitemia (undetectable by microscopy and qPCR). The percentage of positive results detected by Chunap was: 100% (7/7) in cases of reactivation, 91.7% (11/12) in cases of moderate parasitemia, and 41.7% (5/12) in cases of negative parasitemia. Chunap specificity was found to be 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels and urine T. cruzi antigen concentrations (p<0.001). A cut-off of > 105 pg was chosen to determine patients with reactivation of Chagas disease (7/7). Antigenuria levels were 36.08 times (95% CI: 7.28 to 64.88) higher in patients with CD4+ lymphocyte counts below 200/mL (p = 0.016). No significant differences were found in HIV loads and CD8+ lymphocyte counts. Chunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co-infected patients.

  19. Whole-genome association analysis of pork meat pH revealed three significant regions and several potential genes in Finnish Yorkshire pigs.

    PubMed

    Verardo, Lucas L; Sevón-Aimonen, Marja-Liisa; Serenius, Timo; Hietakangas, Ville; Uimari, Pekka

    2017-02-13

    One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin. A bioinformatics analysis was performed to identify the most promising genes in the significant regions related to meat quality. Genome-wide association study (GWAS) revealed three significant chromosomal regions: one on chromosome 3 (39.9 Mb-40.1 Mb) and two on chromosome 15 (58.5 Mb-60.5 Mb and 132 Mb-135 Mb including PRKAG3). A conditional analysis with a significant SNP in the PRKAG3 region, MARC0083357, as a covariate in the model retained the significant SNPs on chromosome 3. Even though linkage disequilibrium was relatively high over a long distance between MARC0083357 and other significant SNPs on chromosome 15, some SNPs retained their significance in the conditional analysis, even in the vicinity of PRKAG3. The significant regions harbored several genes, including two genes involved in cyclic AMP (cAMP) signaling: ADCY9 and CREBBP. Based on functional and transcription factor-gene networks, the most promising candidate genes for meat pH are ADCY9, CREBBP, TRAP1, NRG1, PRKAG3, VIL1, TNS1, and IGFBP5, and the key transcription factors related to these genes are HNF4A, PPARG, and Nkx2-5. Based on SNP association, pathway, and transcription factor analysis, we were able to identify several genes with potential to control muscle cell homeostasis and meat quality. The associated SNPs can be used in selection for better pork. We also showed that post-GWAS analysis reveals important information about the

  20. A nonparametric significance test for sampled networks.

    PubMed

    Elliott, Andrew; Leicht, Elizabeth; Whitmore, Alan; Reinert, Gesine; Reed-Tsochas, Felix

    2018-01-01

    Our work is motivated by an interest in constructing a protein-protein interaction network that captures key features associated with Parkinson's disease. While there is an abundance of subnetwork construction methods available, it is often far from obvious which subnetwork is the most suitable starting point for further investigation. We provide a method to assess whether a subnetwork constructed from a seed list (a list of nodes known to be important in the area of interest) differs significantly from a randomly generated subnetwork. The proposed method uses a Monte Carlo approach. As different seed lists can give rise to the same subnetwork, we control for redundancy by constructing a minimal seed list as the starting point for the significance test. The null model is based on random seed lists of the same length as a minimum seed list that generates the subnetwork; in this random seed list the nodes have (approximately) the same degree distribution as the nodes in the minimum seed list. We use this null model to select subnetworks which deviate significantly from random on an appropriate set of statistics and might capture useful information for a real world protein-protein interaction network. The software used in this paper are available for download at https://sites.google.com/site/elliottande/. The software is written in Python and uses the NetworkX library. ande.elliott@gmail.com or felix.reed-tsochas@sbs.ox.ac.uk. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

  1. A nonparametric significance test for sampled networks

    PubMed Central

    Leicht, Elizabeth; Whitmore, Alan; Reinert, Gesine; Reed-Tsochas, Felix

    2018-01-01

    Abstract Motivation Our work is motivated by an interest in constructing a protein–protein interaction network that captures key features associated with Parkinson’s disease. While there is an abundance of subnetwork construction methods available, it is often far from obvious which subnetwork is the most suitable starting point for further investigation. Results We provide a method to assess whether a subnetwork constructed from a seed list (a list of nodes known to be important in the area of interest) differs significantly from a randomly generated subnetwork. The proposed method uses a Monte Carlo approach. As different seed lists can give rise to the same subnetwork, we control for redundancy by constructing a minimal seed list as the starting point for the significance test. The null model is based on random seed lists of the same length as a minimum seed list that generates the subnetwork; in this random seed list the nodes have (approximately) the same degree distribution as the nodes in the minimum seed list. We use this null model to select subnetworks which deviate significantly from random on an appropriate set of statistics and might capture useful information for a real world protein–protein interaction network. Availability and implementation The software used in this paper are available for download at https://sites.google.com/site/elliottande/. The software is written in Python and uses the NetworkX library. Contact ande.elliott@gmail.com or felix.reed-tsochas@sbs.ox.ac.uk Supplementary information Supplementary data are available at Bioinformatics online. PMID:29036452

  2. HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status.

    PubMed

    Richardson, Lyndsay Ann; El-Zein, Mariam; Ramanakumar, Agnihotram V; Ratnam, Samuel; Sangwa-Lugoma, Ghislain; Longatto-Filho, Adhemar; Cardoso, Marly Augusto; Coutlée, Francois; Franco, Eduardo L

    2015-12-01

    Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. © 2015 American Cancer Society.

  3. Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy.

    PubMed

    Guo, Ye; Lu, Jiade J; Ma, Xuejun; Wang, Biyun; Hong, Xiaonan; Li, Xiaoqiu; Li, Jin

    2008-01-01

    systemic recurrence and died at 13-48 months despite salvage treatment; one patient died of Hemophagocytic Syndrome during radiotherapy after achieving CR from chemotherapy. Three patients with Stage III or IV disease died during chemotherapy or during salvage treatment at 2, 4, and 19 months, respectively. Among the 59 patients who received chemotherapy as their initial treatment, 29, 6, 12, and 12 patients had complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) respectively after chemotherapy. The 2-year overall survival rates for these four groups of patients were 100%, 75%, 60%, and 17%, respectively (P<0.0001). Multivariate analysis revealed that International Prognostic Index (IPI) for Lymphoma, perforation of nasal septum as a presenting symptom, "B" symptoms, ECOG performance, as well as response after chemotherapy, were significant independent prognostic factors for this group of patients. The extent of response after induction chemotherapy is significantly related to the treatment outcome of patients with nasal NK/T-cell lymphoma. CHOP based chemotherapy combined with oral nitrosourea followed by involved field radiotherapy may provide improved treatment results compared to conventional CHOP chemotherapy and radiation. This strategy needs to be optimized and tested in a prospective trial for its efficacy.

  4. Genetic Identification of a PilT Motor in Geobacter sulfurreducens Reveals a Role for Pilus Retraction in Extracellular Electron Transfer

    PubMed Central

    Speers, Allison M.; Schindler, Bryan D.; Hwang, Jihwan; Genc, Aycin; Reguera, Gemma

    2016-01-01

    The metal-reducing bacterium Geobacter sulfurreducens requires the expression of conductive pili to reduce iron oxides and to wire electroactive biofilms, but the role of pilus retraction in these functions has remained elusive. Here we show that of the four PilT proteins encoded in the genome of G. sulfurreducens, PilT3 powered pilus retraction in planktonic cells of a PilT-deficient strain of P. aeruginosa and restored the dense mutant biofilms to wild-type levels. Furthermore, PilT3 and PilT4 rescued the twitching motility defect of the PilT-deficient mutant. However, PilT4 was the only paralog whose inactivation in G. sulfurreducens lead to phenotypes associated with the hyperpiliation of non-retractile mutants such as enhanced adhesion and biofilm-forming abilities. In addition, PilT4 was required to reduce iron oxides. Taken together, the results indicate that PilT4 is the motor ATPase of G. sulfurreducens pili and reveal a previously unrecognized role for pilus retraction in extracellular electron transfer, a strategy that confers on Geobacter spp. an adaptive advantage for metal reduction in the natural environment. PMID:27799920

  5. Surra Sero K-SeT, a new immunochromatographic test for serodiagnosis of Trypanosoma evansi infection in domestic animals.

    PubMed

    Birhanu, Hadush; Rogé, Stijn; Simon, Thomas; Baelmans, Rudy; Gebrehiwot, Tadesse; Goddeeris, Bruno Maria; Büscher, Philippe

    2015-07-30

    Trypanosoma evansi, the causative agent of surra, infects different domestic and wild animals and has a wide geographical distribution. It is mechanically transmitted mainly by haematophagous flies. Parasitological techniques are commonly used for the diagnosis of surra but have limited sensitivity. Therefore, serodiagnosis based on the detection of T. evansi specific antibodies is recommended by the World Organisation for Animal Health (OIE). Recently, we developed a new antibody detection test for the serodiagnosis of T. evansi infection, the Surra Sero K-SeT. Surra Sero K-SeT is an immunochromatographic test (ICT) that makes use of recombinant variant surface glycoprotein rVSG RoTat 1.2, produced in the yeast Pichia pastoris. In this study, we compared the diagnostic accuracy of the Surra Sero K-SeT and the Card Agglutination Test for T. evansi Trypanosomososis (CATT/T. evansi) with immune trypanolysis (TL) as reference test on a total of 806 sera from camels, water buffaloes, horses, bovines, sheep, dogs and alpacas. Test agreement was highest between Surra Sero K-SeT and TL (κ=0.91, 95% CI 0.841-0.979) and somewhat lower between CATT/T. evansi and TL (κ=0.85, 95% CI 0.785-0.922) and Surra Sero K-SeT and CATT/T. evansi (κ=0.81, 95% CI 0.742-0.878). The Surra Sero K-SeT displayed a somewhat lower overall specificity than CATT/T. evansi (94.8% versus 98.3%, χ(2)=13.37, p<0.001) but a considerably higher sensitivity (98.1% versus 84.4%, χ(2)=33.39, p<0.001). We conclude that the Surra Sero K-SeT may become an alternative for the CATT/T. evansi for sensitive detection of antibodies against T. evansi in domestic animals. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Five-Point Likert Items: t Test versus Mann-Whitney-Wilcoxon

    ERIC Educational Resources Information Center

    de Winter, Joost C. F.; Dodou, Dimitra

    2010-01-01

    Likert questionnaires are widely used in survey research, but it is unclear whether the item data should be investigated by means of parametric or nonparametric procedures. This study compared the Type I and II error rates of the "t" test versus the Mann-Whitney-Wilcoxon (MWW) for five-point Likert items. Fourteen population…

  7. 6. Exterior view of Components Test Laboratory (T27), looking southwest. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Exterior view of Components Test Laboratory (T-27), looking southwest. The building wing on the left houses Test Cell 9 (fuel), and that on the right houses the equipment room. The corrugated aluminum shed that is taller than the main building in the left foreground houses a citric acid air pollution control room (also known as scrubber room), the interior of which may be seen in CO-88-A-21. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  8. Significance testing of rules in rule-based models of human problem solving

    NASA Technical Reports Server (NTRS)

    Lewis, C. M.; Hammer, J. M.

    1986-01-01

    Rule-based models of human problem solving have typically not been tested for statistical significance. Three methods of testing rules - analysis of variance, randomization, and contingency tables - are presented. Advantages and disadvantages of the methods are also described.

  9. Transcranial direct current stimulation (tDCS) reveals a dissociation between SNARC and MARC effects: Implication for the polarity correspondence account.

    PubMed

    Di Rosa, Elisa; Bardi, Lara; Umiltà, Carlo; Masina, Fabio; Forgione, Margherita; Mapelli, Daniela

    2017-08-01

    The concept of stimulus response compatibility (SRC) refers to the existence of a privileged association between a specific stimulus feature and a specific response feature. Two examples of SRC are the Spatial Numerical Association of Response Codes (SNARC) and the Markedness Association of Response Codes (MARC) effects. According to the polarity correspondence principle, these two SRC effects occur because of a match between the most salient dimensions of stimulus and response. Specifically, the SNARC effect would be caused by a match between right-sided responses and large numbers, while a match between right-sided responses and even numbers would give rise to the MARC effect. The aim of the present study was to test the validity of the polarity correspondence principle in explaining these two SRC effects. To this end, we applied transcranial direct current stimulation (tDCS) over left and right posterior parietal cortex (PPC), which is thought to be the neural basis of salience processing, during a parity judgement task. Results showed that cathodal tDCS over the PPC significantly reduced the MARC effect but did not affect the SNARC effect, suggesting a dissociation between the two effects. That is, the MARC would rely on a salience processing mechanism, whereas the SNARC would not. Despite this interpretation is in need of further experimental confirmations (i.e., testing different tasks or using different tDCS montages), our results suggest that the polarity correspondence principle can be a plausible explanation only for the MARC effect but not for the SNARC effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing.

    PubMed

    Wang, Yu-Hong; Yu, Xu-Hui; Luo, Shan-Shun; Han, Hui

    2015-01-01

    Ageing brings about the gradual deterioration of the immune system, also known as immunosenescence. The role of non-coding circular RNA in immunosenescence is under studied. Using circular RNA microarray data, we assembled Comparison groups (C1, C2, C3 and C4) that allowed us to compare the circular RNA expression profiles between CD28(+)CD8(+) T cells and CD28(-)CD8(+) T cells isolated from healthy elderly or adult control subjects. Using a step-wise biomathematical strategy, the differentially-expressed circRNAs were identified in C1 (CD28(+)CD8(+) vs CD28(-)CD8(+)T cells in the elderly) and C4 (CD28(-)CD8(+)T cells in the elderly vs in the adult), and the commonly-expressed circRNA species from these profiles were optimized as immunosenescence biomarkers. Four overlapping upregulated circular RNAs (100550, 100783, 101328 and 102592) expressed in cross-comparison between C1 and C4 were validated using quantitative polymerase chain reaction. Of these, only circular RNA100783 exhibited significant validation. None of the down-regulated circular RNAs were expressed in the C1 and the C4 cross-comparisons. Therefore, we further predicted circular RNA100783-targeted miRNA-gene interactions using online DAVID annotation. The analysis revealed that a circular RNA100783-targeted miRNA-mRNA network may be involved in alternative splicing, the production of splice variants, and in the regulation of phosphoprotein expression. Considering the hypothesis of splicing-related biogenesis of circRNAs, we propose that circular RNA100783 may play a role in phosphoprotein-associated functions duringCD28-related CD8(+) T cell ageing. This study is the first to employ circular RNA profiling to investigate circular RNA-micro RNA interactions in ageing human CD8(+)T cell populations and the accompanying loss of CD28 expression. The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global

  11. Edge profiles and limiter tests in Extrap T2

    NASA Astrophysics Data System (ADS)

    Bergsåker, H.; Hedin, G.; Ilyinsky, L.; Larsson, D.; Möller, A.

    New edge profile measurements, including calorimetric measurements of the parallel heat flux, were made in Extrap T2. Test limiters of pure molybdenum and the TZM molybdenum alloy have been exposed in the edge plasma. The surface damage was studied, mainly by microscopy. Tungsten coated graphite probes were also exposed, and the surfaces were studied by microscopy, ion beam analysis and XPS. In this case cracking and mixing of carbon and tungsten at the interface was observed in the most heated areas, whereas carbide formation at the surface was seen in less heated areas. In these tests pure Mo generally fared better than TZM, and thin and cleaner coatings fared better than thicker and less clean.

  12. [Troponin release following exercise test in patients with stable angina pectoris - risk factors and prognostic significance].

    PubMed

    Kokowicz, Piotr; Stec, Sebastian; Flasińska, Katarzyna; Budaj, Andrzej

    2010-04-01

    Increase of troponin (cTn) is a marker of myocardial injury caused by different mechanisms. Exercise testing (ExT) is a useful clinical tool in predicting the risk of myocardial ischemia, especially in patients with multivessel coronary artery disease (CAD), who are more often endangered by medical complications. The test is however limited by its low sensitivity and specificity. To evaluate the reasons for troponin I (cTnI) release after ExT, and to determine its clinical and prognostic implications in patients with stable CAD, referred for elective coronary angiography (ANG). 118 patients without signs of systolic heart failure, referred for planned coronary ANG were included in the analysis. After baseline measurements of NT-proBNP, hsCRP, cTnI, CK-MB levels, maximal ExT was performed, followed by the consecutive measurements of cTnI and CK-MB 12 and 24 hours after examination. All patients underwent coronary ANG and ECHO within 7 days of taking blood samples. All patients were followed up on average for 35.5 months. The cTnI elevation > or = 0.14 ng/mL (> or = 99th percentile value of the reference group) after 24 hours of the ExT was observed in 11 (9%) patients. Predictors of cTnI release in patients after ExT were as follows: ejection fraction < or = 50%, lack or insufficient physical activity, max systolic blood pressure > 160 mm Hg at peak of ExT (OR 6.6, 95% CI 1.2-35.4, p = 0.027; OR 5.5, 95% CI 1.1-28.8, p = 0.04; OR 6.3, 95% CI 1.3-31.6, p = 0.025, respectively). Increase of cTnI after ExT did not correlate with multivessel CAD nor with future adverse clinical events. The cTnI release post ExT is more frequently observed in patients with stable CAD with ejection fraction < or = 50%, low physical activity, and max systolic blood pressure > 160 mm Hg at peak ExT. Post ExT cTnI increase in patients with stable CAD did not correlate with the number of atherosclerotic coronary vessels, and had no prognostic implications. Increase of cTnI after ExT did not

  13. Eight-Year Review of Bordetella pertussis Testing Reveals Seasonal Pattern in the United States.

    PubMed

    Bhatti, Micah M; Rucinski, Stefanea L; Schwab, Jeramy J; Cole, Nicolynn C; Gebrehiwot, Senait A; Patel, Robin

    2017-03-01

    Review of Bordetella pertussis polymerase chain reaction testing from 2007 through 2014 revealed a yearly spike in positivity rates during the summer throughout the United States. Paradoxically, the highest test volumes occurred outside of this time frame, which provides an opportunity for improved test utilization. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Pregnant patients' risk perception of prenatal test results with uncertain fetal clinical significance: ultrasound versus advanced genetic testing.

    PubMed

    Richards, Elliott G; Sangi-Haghpeykar, Haleh; McGuire, Amy L; Van den Veyver, Ignatia B; Fruhman, Gary

    2015-12-01

    A common concern of utilizing prenatal advanced genetic testing is that a result of uncertain clinical significance will increase patient anxiety. However, prenatal ultrasound may also yield findings of uncertain significance, such as 'soft markers' for fetal aneuploidy, or findings with variable prognosis, such as mild ventriculomegaly. In this study we compared risk perception following uncertain test results from each modality. A single survey with repeated measures design was administered to 133 pregnant women. It included 'intolerance of uncertainty' questions, two hypothetical scenarios involving prenatal ultrasound or advanced genetic testing, and response questions. The primary outcome was risk perception score. Risk perception did not vary significantly between ultrasound and genetic scenarios (p = 0.17). The genetic scenario scored a higher accuracy (p = 0.04) but lower sense of empowerment (p = 0.01). Furthermore, patients were more likely to seek additional testing after an ultrasound than after genetic testing (p = 0.05). There were no differences in other secondary outcomes including perception of life-altering consequences and hypothetical worry, anxiety, confusion, or medical care decisions. Our data suggest that uncertain findings on prenatal genetic testing do not elicit a higher perception of risk or anxiety when compared to ultrasound findings of comparable uncertainty. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  15. EBOLA Ag K-SeT rapid test: field evaluation in Sierra Leone.

    PubMed

    Colavita, F; Biava, M; Mertens, P; Gilleman, Q; Borlon, C; Delli Guanti, M; Petrocelli, A; Cataldi, G; Kamara, A T; Kamara, S A; Konneh, K; Vincenti, D; Castilletti, C; Abdurahman, S; Mirazimi, A; Capobianchi, M R; Ippolito, G; Miccio, R; Di Caro, A

    2018-06-01

    Efficient interruption of Ebola virus disease (EVD) transmission chains critically depends on reliable and fast laboratory diagnosis. We evaluated the performance of the EBOLA Virus Antigen Detection K-SeT (EBOLA Ag K-SeT), a new rapid diagnostic antigen test in field settings. The study was conducted in a field laboratory located in Freetown (Sierra Leone) by the Italian National Institute for Infectious Diseases 'L. Spallanzani' and the EMERGENCY Onlus NGO. The EBOLA Ag K-SeT was tested on 210 residual plasma samples (EVD prevalence 50%) from patients hospitalized at the EMERGENCY Ebola treatment center in Goderich (Freetown), comparing the results with quantitative real-time PCR. Overall, the sensitivity of EBOLA Ag K-SeT was 88.6% (95% confidence interval (CI), 82.5-94.7), and the corresponding specificity was 98.1% (95% CI, 95.5-100.7). The positive and negative predictive values were 97.9% (95% CI, 95.0-100.8) and 89.6% (95% CI, 84-95.2), respectively. The sensitivity strongly increased up to 98.7% (95% CI, 96.1-101.2) for those samples with high virus load (≥6.2 log RNA copies/mL). Our results suggest that EBOLA Ag K-SeT could represent a new effective diagnostic tool for EVD, meeting a need for resource-poor settings and rapid diagnosis for individuals with suspected EVD. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Pulse transit time reveals drug kinetics on vascular changes affected by propofol.

    PubMed

    Lan, Yuan-Chun; Shen, Ching-Hui; Kang, Hsung-Ming; Chong, Fok-Ching

    2012-01-01

    Pulse transit time (PTT) is the duration in which a pulse wave travels between two arterial sites within the same cardiac cycle. The aim of our study is to use PTT to examine propofol's effects on the vascular system. Methods. We collected data from 50 healthy women, between 28 and 51 years old, who underwent gynaecological surgery under general anaesthesia. The general anaesthesia was induced with propofol injection (2 mg/kg). PTT measurements were obtained from the R-wave of electrocardiogram and the pulse wave of photoplethysmograph. Two PTT values were obtained; one before (the control) and the other after propofol injection. The results were analysed by Student's t-test. Results. After propofol injection, the PTT was prolonged. The change in the PTT value from that of baseline was significant statistically (P < 0.05, by Student's t-test). The PTT change over time correlated with the degree of vasodilatation over time. Monitoring of PTT not only revealed the magnitude of vascular changes but also demonstrated the onset of vascular dilation, its peak and duration. We conclude that PTT is a useful guide in monitoring the drug kinetics of propofol.

  17. An improved method to set significance thresholds for β diversity testing in microbial community comparisons.

    PubMed

    Gülay, Arda; Smets, Barth F

    2015-09-01

    Exploring the variation in microbial community diversity between locations (β diversity) is a central topic in microbial ecology. Currently, there is no consensus on how to set the significance threshold for β diversity. Here, we describe and quantify the technical components of β diversity, including those associated with the process of subsampling. These components exist for any proposed β diversity measurement procedure. Further, we introduce a strategy to set significance thresholds for β diversity of any group of microbial samples using rarefaction, invoking the notion of a meta-community. The proposed technique was applied to several in silico generated operational taxonomic unit (OTU) libraries and experimental 16S rRNA pyrosequencing libraries. The latter represented microbial communities from different biological rapid sand filters at a full-scale waterworks. We observe that β diversity, after subsampling, is inflated by intra-sample differences; this inflation is avoided in the proposed method. In addition, microbial community evenness (Gini > 0.08) strongly affects all β diversity estimations due to bias associated with rarefaction. Where published methods to test β significance often fail, the proposed meta-community-based estimator is more successful at rejecting insignificant β diversity values. Applying our approach, we reveal the heterogeneous microbial structure of biological rapid sand filters both within and across filters. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  18. [Words before actions- the significance of counselling in the Praena-Test era].

    PubMed

    Tschudin, Sibil

    2014-04-23

    Due to new offers in prenatal diagnostics pregnant women are forced to make choices. In Switzerland physicians are obliged to inform previous to prenatal tests and to obtain informed consent. Considering the complexity of this information and the consequences of a positive result, counselling is challenging, especially in an intercultural context. A questionnaire-based study compared information processing, test interpretation and emotional response of pregnant women from Switzerland and adjacent countries with Turkish women. Knowledge of the latter was significantly lower and they found counselling more unsettling, but their acceptance of prenatal tests was significantly higher. An empathetic approach and the right words are decisive, and counselling will even gain importance when considering the increase in options patients are confronted with.

  19. Combined metabonomic and quantitative real-time PCR analyses reveal systems metabolic changes in Jurkat T-cells treated with HIV-1 Tat protein.

    PubMed

    Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

    2012-11-02

    HIV-1 Tat protein is released by infected cells and can affect bystander uninfected T cells and induce numerous biological responses which contribute to its pathogenesis. To elucidate the complex pathogenic mechanism, we conducted a comprehensive investigation on Tat protein-related extracellular and intracellular metabolic changes in Jurkat T-cells using combined gas chromatography-mass spectrometry (GC-MS), reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and a hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS)-based metabonomics approach. Quantitative real-time PCR (qRT-PCR) analyses were further employed to measure expressions of several relevant enzymes together with perturbed metabolic pathways. Combined metabonomic and qRT-PCR analyses revealed that HIV-1 Tat caused significant and comprehensive metabolic changes, as represented by significant changes of 37 metabolites and 10 relevant enzymes in HIV-1 Tat-treated cells. Using MetaboAnalyst 2.0, it was found that 11 pathways (Impact-value >0.10) among the regulated pathways were acutely perturbed, including sphingolipid metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, inositol phosphate metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism, pentose phosphate pathway, glycerophospholipid metabolism, glycolysis or gluconeogenesis. These results provide metabolic evidence of the complex pathogenic mechanism of HIV-1 Tat protein as a "viral toxin", and would help obligate Tat protein as "an important target" for therapeutic intervention and vaccine development.

  20. 3D: diversity, dynamics, differential testing - a proposed pipeline for analysis of next-generation sequencing T cell repertoire data.

    PubMed

    Zhang, Li; Cham, Jason; Paciorek, Alan; Trager, James; Sheikh, Nadeem; Fong, Lawrence

    2017-02-27

    Cancer immunotherapy has demonstrated significant clinical activity in different cancers. T cells represent a crucial component of the adaptive immune system and are thought to mediate anti-tumoral immunity. Antigen-specific recognition by T cells is via the T cell receptor (TCR) which is unique for each T cell. Next generation sequencing (NGS) of the TCRs can be used as a platform to profile the T cell repertoire. Though there are a number of software tools available for processing repertoire data by mapping antigen receptor segments to sequencing reads and assembling the clonotypes, most of them are not designed to track and examine the dynamic nature of the TCR repertoire across multiple time points or between different biologic compartments (e.g., blood and tissue samples) in a clinical context. We integrated different diversity measures to assess the T cell repertoire diversity and examined the robustness of the diversity indices. Among those tested, Clonality was identified for its robustness as a key metric for study design and the first choice to measure TCR repertoire diversity. To evaluate the dynamic nature of T cell clonotypes across time, we utilized several binary similarity measures (such as Baroni-Urbani and Buser overlap index), relative clonality and Morisita's overlap index, as well as the intraclass correlation coefficient, and performed fold change analysis, which was further extended to investigate the transition of clonotypes among different biological compartments. Furthermore, the application of differential testing enabled the detection of clonotypes which were significantly changed across time. By applying the proposed "3D" analysis pipeline to the real example of prostate cancer subjects who received sipuleucel-T, an FDA-approved immunotherapy, we were able to detect changes in TCR sequence frequency and diversity thus demonstrating that sipuleucel-T treatment affected TCR repertoire in blood and in prostate tissue. We also found that

  1. SSU rDNA sequence diversity and seasonally differentiated distribution of nanoplanktonic ciliates in neritic Bohai and Yellow Seas as revealed by T-RFLP.

    PubMed

    Dong, Jun; Shi, Fei; Li, Han; Zhang, Xiaoming; Hu, Xiaozhong; Gong, Jun

    2014-01-01

    Nanociliates have been frequently found to be important players in the marine microbial loop, however, little is known about their diversity and distribution in coastal ecosystems. We investigated the molecular diversity and distribution patterns of nanoplanktonic oligotrich and choreotrich (OC) ciliates in surface water of three neritic basins of northern China, the South Yellow Sea (SYS), North Yellow Sea (NYS), and Bohai Sea (BS) in June and November 2011. SSU rRNA gene clone libraries generated from three summertime samples (sites B38, B4 and H8) were analyzed and revealed a large novel ribotype diversity, of which many were low-abundant phylotypes belonging to the subclass Oligotrichia, but divergent from described morphospecies. Based on the data of terminal-restriction fragment length polymorphism (T-RFLP) analysis of all 35 samples, we found that the T-RF richness was generally higher in the SYS than in the BS, and negatively correlated with the molar ratio of P to Si. Overall, multidimensional scaling and permutational multivariate analysis of variance of the community turnover demonstrated a distinct seasonal pattern but no basin-to-basin differentiation across all samples. Nevertheless, significant community differences among basins were recognized in the winter dataset. Mantel tests showed that the environmental factors, P:Si ratio, water temperature and concentration of dissolved oxygen (DO), determined the community across all samples. However, both biogeographic distance and environment shaped the community in winter, with DO being the most important physicochemical factor. Our results indicate that the stoichiometric ratio of P:Si is a key factor, through which the phytoplankton community may be shaped, resulting in a cascade effect on the diversity and community composition of OC nanociliates in the N-rich, Si-limited coastal surface waters, and that the Yellow Sea Warm Current drives the nanociliate community, and possibly the microbial food webs

  2. Test-retest reliability of the Clinical Learning Environment, Supervision and Nurse Teacher (CLES + T) scale.

    PubMed

    Gustafsson, Margareta; Blomberg, Karin; Holmefur, Marie

    2015-07-01

    The Clinical Learning Environment, Supervision and Nurse Teacher (CLES + T) scale evaluates the student nurses' perception of the learning environment and supervision within the clinical placement. It has never been tested in a replication study. The aim of the present study was to evaluate the test-retest reliability of the CLES + T scale. The CLES + T scale was administered twice to a group of 42 student nurses, with a one-week interval. Test-retest reliability was determined by calculations of Intraclass Correlation Coefficients (ICCs) and weighted Kappa coefficients. Standard Error of Measurements (SEM) and Smallest Detectable Difference (SDD) determined the precision of individual scores. Bland-Altman plots were created for analyses of systematic differences between the test occasions. The results of the study showed that the stability over time was good to excellent (ICC 0.88-0.96) in the sub-dimensions "Supervisory relationship", "Pedagogical atmosphere on the ward" and "Role of the nurse teacher". Measurements of "Premises of nursing on the ward" and "Leadership style of the manager" had lower but still acceptable stability (ICC 0.70-0.75). No systematic differences occurred between the test occasions. This study supports the usefulness of the CLES + T scale as a reliable measure of the student nurses' perception of the learning environment within the clinical placement at a hospital. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet-Based System to Improve Prevention of Mother-to-Child Transmission of HIV.

    PubMed

    Bull, Sheana; Thomas, Deborah Sk; Nyanza, Elias C; Ngallaba, Sospatro E

    2018-01-15

    The prevention of mother-to-child transmission (PMTCT) of HIV requires innovative solutions. Although routine monitoring is effective in some areas, standardized and easy-to-scale solutions to identify and monitor pregnant women, test them for HIV, and treat them and their children is still lacking. Mobile health (mHealth) offers opportunities for surveillance and reporting in rural areas of low- and middle-income countries. The aim of this study was to document the preliminary impacts of the Tanzania Health Information Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT care delivery and capacity building in a rural area of Tanzania. We developed T-HIT as a tablet-based system for an electronic data collection system designed to capture and report PMTCT data during antenatal, delivery, and postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a pilot randomized trial comparing seven sites using T-HIT assigned at random to seven control sites; all sites maintained standard paper record-keeping during the pilot intervention period. We compared numbers of antenatal visits, number of HIV tests administered, and women testing positive across all sites. Health workers recorded data from antenatal visits for 1530 women; of these, 695 (45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of lack of reagent, which is not captured on paper logs. There was no difference in the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We observed a significant postintervention increase in the numbers of women testing positive for HIV compared with the preintervention period (P=.04), but this was likely not attributable to the T-HIT system. T-HIT had a high degree of acceptability and feasibility and is perceived as useful by health workers, who documented more antenatal visits during the pilot intervention

  4. Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet-Based System to Improve Prevention of Mother-to-Child Transmission of HIV

    PubMed Central

    Bull, Sheana; Nyanza, Elias C; Ngallaba, Sospatro E

    2018-01-01

    Background The prevention of mother-to-child transmission (PMTCT) of HIV requires innovative solutions. Although routine monitoring is effective in some areas, standardized and easy-to-scale solutions to identify and monitor pregnant women, test them for HIV, and treat them and their children is still lacking. Mobile health (mHealth) offers opportunities for surveillance and reporting in rural areas of low- and middle-income countries. Objective The aim of this study was to document the preliminary impacts of the Tanzania Health Information Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT care delivery and capacity building in a rural area of Tanzania. Methods We developed T-HIT as a tablet-based system for an electronic data collection system designed to capture and report PMTCT data during antenatal, delivery, and postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a pilot randomized trial comparing seven sites using T-HIT assigned at random to seven control sites; all sites maintained standard paper record-keeping during the pilot intervention period. We compared numbers of antenatal visits, number of HIV tests administered, and women testing positive across all sites. Results Health workers recorded data from antenatal visits for 1530 women; of these, 695 (45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of lack of reagent, which is not captured on paper logs. There was no difference in the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We observed a significant postintervention increase in the numbers of women testing positive for HIV compared with the preintervention period (P=.04), but this was likely not attributable to the T-HIT system. Conclusions T-HIT had a high degree of acceptability and feasibility and is perceived as useful by health workers, who documented more

  5. Logrank test and Interval Overlap Test for Bactericera cockerelli (Hemiptera: Triozidae) under different fertilization treatments for 7705 tomato hybrid.

    PubMed

    Vargas-Madríz, Haidel; Bautista-Martínez, Néstor; Vera-Graziano, Jorge; Sánchez-García, Prometeo; García-Gutiérrez, Cipriano; Sánchez-Soto, Saúl; García-Avila, Clemente de Jesús

    2014-01-01

    It is known that some nutrients can have both negative and positive effects on some populations of insects. To test this, the Logrank test and the Interval Overlap Test were evaluated for two crop cycles (February-May and May-August) of the 7705 tomato hybrid, and the effect on the psyllid, Bactericera cockerelli (Sulc.) (Hemiptera: Triozidae), was examined under greenhouse conditions. Tomato plants were in polythene bags and irrigated with the following solutions: T1-Steiner solution, T2-Steiner solution with nitrogen reduced to 25%, T3-Steiner solution with potassium reduced to 25%, and T4-Steiner solution with calcium reduced to 25%. In the Logrank test, a significant difference was found when comparing the survival parameters of B. cockerelli generated from the treatment cohorts: T1-T2; T1-T3; T1-T4; T2-T3; and T3-T4, while no significant differences were found in the T2-T4 comparison in the February-May cycle. In the May-August cycle, significant differences were found when comparing the survival parameters generated from the treatment cohorts: T1-T2; T1-T3; and T1-T4, while no significant differences were found in the T2-T3; T2-T4; and T3-T4 comparisons of survival parameters of B. cockerelli fed with the 7705 tomato hybrid. Also, the Interval Overlap Test was done on the treatment cohorts (T1, T2, T3, and T4) in the February-May and May-August cycles. T1 and T2 compare similarly in both cycles when feeding on the treatments up to 36 d. Similarly, in T1 and T3, the behavior of the insect is similar when feeding on the treatments up to 40 and 73 d, respectively. Comparisons T2-T3 and T2-T4 are similar when feeding on both treatments up to 42, 38 and 37, 63 d, respectively. Finally, the T3-T4 comparison was similar when feeding in both treatments up to 20 and 46 d, respectively. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

  6. P. aeruginosa PilT Structures with and without Nucleotide Reveal a Dynamic Type IV Pilus Retraction Motor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Misic, Ana M.; Satyshur, Kenneth A.; Forest, Katrina T.

    Type IV pili are bacterial extracellular filaments that can be retracted to create force and motility. Retraction is accomplished by the motor protein PilT. Crystal structures of Pseudomonas aeruginosa PilT with and without bound {beta},{gamma}-methyleneadenosine-5{prime}-triphosphate have been solved at 2.6 {angstrom} and 3.1 {angstrom} resolution, respectively, revealing an interlocking hexamer formed by the action of a crystallographic 2-fold symmetry operator on three subunits in the asymmetric unit and held together by extensive ionic interactions. The roles of two invariant carboxylates, Asp Box motif Glu163 and Walker B motif Glu204, have been assigned to Mg{sup 2+} binding and catalysis, respectively. Themore » nucleotide ligands in each of the subunits in the asymmetric unit of the {beta},{gamma}-methyleneadenosine-5{prime}-triphosphate-bound PilT are not equally well ordered. Similarly, the three subunits in the asymmetric unit of both structures exhibit differing relative conformations of the two domains. The 12{sup o} and 20{sup o} domain rotations indicate motions that occur during the ATP-coupled mechanism of the disassembly of pili into membrane-localized pilin monomers. Integrating these observations, we propose a three-state 'Ready, Active, Release' model for the action of PilT.« less

  7. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

    PubMed

    Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

    2015-01-01

    A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

  8. Tests of English Language as Significant Thresholds for College-Bound Chinese and the Washback of Test-Preparation

    ERIC Educational Resources Information Center

    Matoush, Marylou M.; Fu, Danling

    2012-01-01

    Tests of English language mark significantly high thresholds for all college-bound students in the People's Republic of China. Many Chinese students hope to seek their fortunes at universities in the United States, or other English speaking countries. These students spend long hours, year after year, in test-preparation centres in order to develop…

  9. Effect of mirror therapy with tDCS on functional recovery of the upper extremity of stroke patients.

    PubMed

    Cho, Hyuk-Shin; Cha, Hyun-Gyu

    2015-04-01

    [Purpose] This study aimed to determine the effect of mirror therapy (MT) with transcranial direct current stimulation (tDCS) on the recovery of the upper extremity function of chronic stroke patients. [Subjects] Twenty-seven patients at least 6 months after stroke onset were divided randomly into an experimental group (14 patients) and a control group (13 patients). [Methods] All subjects received tDCS for 20 min followed by a 5 min rest. Then the experimental group received MT while the control group conducted the same exercises as the experimental group using a mirror that did not show the non-paretic upper extremity. The groups performed the same exercises for 20 min. All subjects received this intervention for 45-min three times a week for 6 weeks. [Results] After the intervention, the experimental group showed significant improvements in the box and block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA), and a significant decrease in the Jebsen-Taylor test. The control group showed a significant increase in grip strength after the intervention, and a significant decrease in the Jebsen-Taylor test. Comparison of the result after the intervention revealed that the experimental group showed more significant increases in the BBT and grip strength than the control group. [Conclusion] These results show that MT with tDCS has a positive effect on the functional recovery of the upper extremity of stroke patients, through activating motor regions in the brain, and thus plays an important role in recovery of neuroplasticity.

  10. Immunopathological effect of the mycotoxins cyclopiazonic acid and T-2 toxin on broiler chicken.

    PubMed

    Kamalavenkatesh, P; Vairamuthu, S; Balachandran, C; Manohar, B Murali; raj, G Dhinakar

    2005-02-01

    Forty, newly hatched, unsexed broiler chicks were fed diets containing 10 ppm cyclopiazonic acid (CPA) and 1 ppm T-2 toxin (T2) either individually or in combination for 28 days to study the immunopathological effects. Lymphoid organs revealed lymphocytolysis and lymphoid depletion in all toxin fed birds. Thymic and splenic CD+4 and CD+8 lymphocytes decreased significantly (p<0.01) in toxin fed birds when compared to the control. Thymic CD+8 lymphocytes of T2 and CPA-T2 showed significant (p<0.01) decrease from that of CPA and control groups. Splenic CD+4 and CD+8 lymphocytes showed significant (p<0.01) decrease in CPA and CPA-T2 fed groups when compared to the control. The T2 group did not differ significantly from that of control. The stimulation index (SI) of splenocytes to concavalin A revealed significant (p<0.01) decrease in all toxin fed birds. Significant (p<0.01) decrease were observed for the haemagglutination inhibition (HI) titres to Newcastle disease virus vaccine F strain (NDV) of birds fed CPA, T2 and in combination. Significant (p<0.01) interaction was found for lymphocyte subsets, SI and HI titres to NDV. The study indicated the immunosuppressive effect of these toxins either alone or in combination in broiler chicks.

  11. Genetic alteration of the metal/redox modulation of Cav3.2 T-type calcium channel reveals its role in neuronal excitability.

    PubMed

    Voisin, Tiphaine; Bourinet, Emmanuel; Lory, Philippe

    2016-07-01

    In this study, we describe a new knock-in (KI) mouse model that allows the study of the H191-dependent regulation of T-type Cav3.2 channels. Sensitivity to zinc, nickel and ascorbate of native Cav3.2 channels is significantly impeded in the dorsal root ganglion (DRG) neurons of this KI mouse. Importantly, we describe that this H191-dependent regulation has discrete but significant effects on the excitability properties of D-hair (down-hair) cells, a sub-population of DRG neurons in which Cav3.2 currents prominently regulate excitability. Overall, this study reveals that the native H191-dependent regulation of Cav3.2 channels plays a role in the excitability of Cav3.2-expressing neurons. This animal model will be valuable in addressing the potential in vivo roles of the trace metal and redox modulation of Cav3.2 T-type channels in a wide range of physiological and pathological conditions. Cav3.2 channels are T-type voltage-gated calcium channels that play important roles in controlling neuronal excitability, particularly in dorsal root ganglion (DRG) neurons where they are involved in touch and pain signalling. Cav3.2 channels are modulated by low concentrations of metal ions (nickel, zinc) and redox agents, which involves the histidine 191 (H191) in the channel's extracellular IS3-IS4 loop. It is hypothesized that this metal/redox modulation would contribute to the tuning of the excitability properties of DRG neurons. However, the precise role of this H191-dependent modulation of Cav3.2 channel remains unresolved. Towards this goal, we have generated a knock-in (KI) mouse carrying the mutation H191Q in the Cav3.2 protein. Electrophysiological studies were performed on a subpopulation of DRG neurons, the D-hair cells, which express large Cav3.2 currents. We describe an impaired sensitivity to zinc, nickel and ascorbate of the T-type current in D-hair neurons from KI mice. Analysis of the action potential and low-threshold calcium spike (LTCS) properties revealed

  12. Identifying Significant Changes in Cerebrovascular Reactivity to Carbon Dioxide.

    PubMed

    Sobczyk, O; Crawley, A P; Poublanc, J; Sam, K; Mandell, D M; Mikulis, D J; Duffin, J; Fisher, J A

    2016-05-01

    Changes in cerebrovascular reactivity can be used to assess disease progression and response to therapy but require discrimination of pathology from normal test-to-test variability. Such variability is due to variations in methodology, technology, and physiology with time. With uniform test conditions, our aim was to determine the test-to-test variability of cerebrovascular reactivity in healthy subjects and in patients with known cerebrovascular disease. Cerebrovascular reactivity was the ratio of the blood oxygen level-dependent MR imaging response divided by the change in carbon dioxide stimulus. Two standardized cerebrovascular reactivity tests were conducted at 3T in 15 healthy men (36.7 ± 16.1 years of age) within a 4-month period and were coregistered into standard space to yield voxelwise mean cerebrovascular reactivity interval difference measures, composing a reference interval difference atlas. Cerebrovascular reactivity interval difference maps were prepared for 11 male patients. For each patient, the test-retest difference of each voxel was scored statistically as z-values of the corresponding voxel mean difference in the reference atlas and then color-coded and superimposed on the anatomic images to create cerebrovascular reactivity interval difference z-maps. There were no significant test-to-test differences in cerebrovascular reactivity in either gray or white matter (mean gray matter, P = .431; mean white matter, P = .857; paired t test) in the healthy cohort. The patient cerebrovascular reactivity interval difference z-maps indicated regions where cerebrovascular reactivity increased or decreased and the probability that the changes were significant. Accounting for normal test-to-test differences in cerebrovascular reactivity enables the assessment of significant changes in disease status (stability, progression, or regression) in patients with time. © 2016 by American Journal of Neuroradiology.

  13. Bacteriophage T7 RNA polymerase-based expression in Pichia pastoris.

    PubMed

    Hobl, Birgit; Hock, Björn; Schneck, Sandra; Fischer, Reinhard; Mack, Matthias

    2013-11-01

    A novel Pichia pastoris expression vector (pEZT7) for the production of recombinant proteins employing prokaryotic bacteriophage T7 RNA polymerase (T7 RNAP) (EC 2.7.7.6) and the corresponding promoter pT7 was constructed. The gene for T7 RNAP was stably introduced into the P. pastoris chromosome 2 under control of the (endogenous) constitutive P. pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter (pGAP). The gene product T7 RNAP was engineered to contain a nuclear localization signal, which directed recombinant T7 RNAP to the P. pastoris nucleus. To promote translation of uncapped T7 RNAP derived transcripts, the internal ribosomal entry site from hepatitis C virus (HCV-IRES) was inserted directly upstream of the multiple cloning site of pEZT7. A P. pastoris autonomous replicating sequence (PARS1) was integrated into pEZT7 enabling propagation and recovery of plasmids from P. pastoris. Rapid amplification of 5' complementary DNA ends (5' RACE) experiments employing the test plasmid pEZT7-EGFP revealed that transcripts indeed initiated at pT7. HCV-IRES mediated translation of the latter mRNAs, however, was not observed. Surprisingly, HCV-IRES and the reverse complement of PARS1 (PARS1rc) were both found to display significant promoter activity as shown by 5' RACE. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849+10kbC>T: Significance for geneticists

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gilbert, F.; Li, Zhen; Arzimanoglou, I.

    We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kbC>T as homozygotes or compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic-sufficient and sweat test-negative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negative/inconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+10kbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possiblymore » for CF carrier screening in the general population. 19 refs., 1 tab.« less

  15. Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients

    PubMed Central

    Castro-Sesquen, Yagahira E.; Gilman, Robert H.; Mejia, Carolina; Clark, Daniel E.; Choi, Jeong; Reimer-McAtee, Melissa J.; Castro, Rosario; Valencia-Ayala, Edward; Flores, Jorge; Bowman, Natalie; Castillo-Neyra, Ricardo; Torrico, Faustino; Liotta, Lance; Bern, Caryn; Luchini, Alessandra

    2016-01-01

    Background Early diagnosis of reactivated Chagas disease in HIV patients could be lifesaving. In Latin America, the diagnosis is made by microscopical detection of the T. cruzi parasite in the blood; a diagnostic test that lacks sensitivity. This study evaluates if levels of T. cruzi antigens in urine, determined by Chunap (Chagas urine nanoparticle test), are correlated with parasitemia levels in T. cruzi/HIV co-infected patients. Methodology/Principal Findings T. cruzi antigens in urine of HIV patients (N = 55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. Reactivation of Chagas disease was defined by the observation of parasites in blood by microscopy. Parasitemia levels in patients with serology positive for Chagas disease were classified as follows: High parasitemia or reactivation of Chagas disease (detectable parasitemia by microscopy), moderate parasitemia (undetectable by microscopy but detectable by qPCR), and negative parasitemia (undetectable by microscopy and qPCR). The percentage of positive results detected by Chunap was: 100% (7/7) in cases of reactivation, 91.7% (11/12) in cases of moderate parasitemia, and 41.7% (5/12) in cases of negative parasitemia. Chunap specificity was found to be 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels and urine T. cruzi antigen concentrations (p<0.001). A cut-off of > 105 pg was chosen to determine patients with reactivation of Chagas disease (7/7). Antigenuria levels were 36.08 times (95% CI: 7.28 to 64.88) higher in patients with CD4+ lymphocyte counts below 200/mL (p = 0.016). No significant differences were found in HIV loads and CD8+ lymphocyte counts. Conclusion Chunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co

  16. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia

    PubMed Central

    Kiel, Mark J.; Velusamy, Thirunavukkarasu; Rolland, Delphine; Sahasrabuddhe, Anagh A.; Chung, Fuzon; Bailey, Nathanael G.; Schrader, Alexandra; Li, Bo; Li, Jun Z.; Ozel, Ayse B.; Betz, Bryan L.; Miranda, Roberto N.; Medeiros, L. Jeffrey; Zhao, Lili; Herling, Marco

    2014-01-01

    The comprehensive genetic alterations underlying the pathogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown. To address this, we performed whole-genome sequencing (WGS), whole-exome sequencing (WES), high-resolution copy-number analysis, and Sanger resequencing of a large cohort of T-PLL. WGS and WES identified novel mutations in recurrently altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2. Strikingly, WGS and/or WES showed largely mutually exclusive mutations affecting IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%). Notably, gain-of-function IL2RG mutations are novel and have not been reported in any form of cancer. Further, high-frequency mutations in STAT5B have not been previously reported in T-PLL. Functionally, IL2RG-JAK1-JAK3-STAT5B mutations led to signal transducer and activator of transcription 5 (STAT5) hyperactivation, transformed Ba/F3 cells resulting in cytokine-independent growth, and/or enhanced colony formation in Jurkat T cells. Importantly, primary T-PLL cells exhibited constitutive activation of STAT5, and targeted pharmacologic inhibition of STAT5 with pimozide induced apoptosis in primary T-PLL cells. These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL. These findings offer opportunities for novel targeted therapies in this aggressive leukemia. PMID:24825865

  17. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia.

    PubMed

    Kiel, Mark J; Velusamy, Thirunavukkarasu; Rolland, Delphine; Sahasrabuddhe, Anagh A; Chung, Fuzon; Bailey, Nathanael G; Schrader, Alexandra; Li, Bo; Li, Jun Z; Ozel, Ayse B; Betz, Bryan L; Miranda, Roberto N; Medeiros, L Jeffrey; Zhao, Lili; Herling, Marco; Lim, Megan S; Elenitoba-Johnson, Kojo S J

    2014-08-28

    The comprehensive genetic alterations underlying the pathogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown. To address this, we performed whole-genome sequencing (WGS), whole-exome sequencing (WES), high-resolution copy-number analysis, and Sanger resequencing of a large cohort of T-PLL. WGS and WES identified novel mutations in recurrently altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2. Strikingly, WGS and/or WES showed largely mutually exclusive mutations affecting IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%). Notably, gain-of-function IL2RG mutations are novel and have not been reported in any form of cancer. Further, high-frequency mutations in STAT5B have not been previously reported in T-PLL. Functionally, IL2RG-JAK1-JAK3-STAT5B mutations led to signal transducer and activator of transcription 5 (STAT5) hyperactivation, transformed Ba/F3 cells resulting in cytokine-independent growth, and/or enhanced colony formation in Jurkat T cells. Importantly, primary T-PLL cells exhibited constitutive activation of STAT5, and targeted pharmacologic inhibition of STAT5 with pimozide induced apoptosis in primary T-PLL cells. These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL. These findings offer opportunities for novel targeted therapies in this aggressive leukemia. © 2014 by The American Society of Hematology.

  18. Five New Records of Soil-Derived Trichoderma in Korea: T. albolutescens, T. asperelloides, T. orientale, T. spirale, and T. tomentosum

    PubMed Central

    Jang, Seokyoon; Jang, Yeongseon; Kim, Chul-Whan; Lee, Hanbyul; Hong, Joo-Hyun; Heo, Young Mok; Lee, Young Min; Lee, Dong Wan; Lee, Hyang Burm

    2017-01-01

    Despite the huge worldwide diversity of Trichoderma (Hypocreaceae, Ascomycota), only about 22 species have been reported in Korea. Thus, between 2013 and 2015, soil-derived Trichoderma spp. were isolated to reveal the diversity of Korean Trichoderma. Phylogenetic analysis of translation elongation factor 1 alpha gene was used for identification. Among the soil-derived Trichoderma, Trichoderma albolutescens, T. asperelloides, T. orientale, T. spirale, and T. tomentosum have not been previously reported in Korea. Thus, we report the five Trichoderma species as new in Korea with morphological descriptions and images. PMID:28435347

  19. The 3T3 neutral red uptake phototoxicity test: practical experience and implications for phototoxicity testing--the report of an ECVAM-EFPIA workshop.

    PubMed

    Ceridono, Mara; Tellner, Pär; Bauer, Daniel; Barroso, João; Alépée, Nathalie; Corvi, Raffaella; De Smedt, Ann; Fellows, Mick D; Gibbs, Neil K; Heisler, Eckhard; Jacobs, Abigail; Jirova, Dagmar; Jones, David; Kandárová, Helena; Kasper, Peter; Akunda, Jacqueline Kinyamu; Krul, Cyrille; Learn, Douglas; Liebsch, Manfred; Lynch, Anthony M; Muster, Wolfgang; Nakamura, Kazuichi; Nash, J Frank; Pfannenbecker, Uwe; Phillips, Gareth; Robles, Catherine; Rogiers, Vera; Van De Water, Femke; Liminga, Ulla Wändel; Vohr, Hans-Werner; Wattrelos, Olivier; Woods, Julie; Zuang, Valérie; Kreysa, Joachim; Wilcox, Phil

    2012-08-01

    This is the report from the "ECVAM-EFPIA workshop on 3T3 NRU Phototoxicity Test: Practical Experience and Implications for Phototoxicity Testing", jointly organized by ECVAM and EFPIA and held on the 25-27 October 2010 in Somma Lombardo, Italy. The European Centre for the Validation of Alternative Methods (ECVAM) was established in 1991 within the European Commission Joint Research, based on a Communication from the European Commission (1991). The main objective of ECVAM is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine and replace the use of laboratory animals. The European Federation of Pharmaceuticals Industries and Association (EFPIA) represent the pharmaceutical industry operating in Europe. Through its direct membership of 31 national associations and 40 leading pharmaceutical companies, EFPIA is the voice on the EU scene of 2200 companies committed to researching, developing and bringing to patients new medicines that improve health and the quality of life around the world. The workshop, co-chaired by Joachim Kreysa (ECVAM) and Phil Wilcox (GSK, EFPIA) involved thirty-five experts from academia, regulatory authorities and industry, invited to contribute with their experiences in the field of phototoxicology. The main objectives of the workshop were: -to present 'in use' experience of the pharmaceutical industry with the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU-PT), -to discuss why it differs from the results in the original validation exercise, -to discuss technical issues and consider ways to improve the usability of the 3T3 NRU-PT for (non-topical) pharmaceuticals, e.g., by modifying the threshold of chemical light absorption to trigger photo-toxicological testing, and by modifying technical aspects of the assay, or adjusting the criteria used to classify a positive response. During the workshop, the assay methodology was reviewed by comparing the OECD

  20. Inter- and Intra-individual Variability in Response to Transcranial Direct Current Stimulation (tDCS) at Varying Current Intensities.

    PubMed

    Chew, Taariq; Ho, Kerrie-Anne; Loo, Colleen K

    2015-01-01

    Translation of transcranial direct current stimulation (tDCS) from research to clinical practice is hindered by a lack of consensus on optimal stimulation parameters, significant inter-individual variability in response, and in sufficient intra-individual reliability data. Inter-individual differences in response to anodal tDCS at a range of current intensities were explored. Intra-individual reliability in response to anodal tDCS across two identical sessions was also investigated. Twenty-nine subjects participated in a crossover study. Anodal-tDCS using four different current intensities (0.2, 0.5, 1 and 2 mA), with an anode size of 16 cm2, was tested. The 0.5 mA condition was repeated to assess intra-individual variability. TMS was used to elicit 40 motor-evoked potentials (MEPs) before 10 min of tDCS, and 20 MEPs at four time-points over 30 min following tDCS. ANOVA revealed no main effect of TIME for all conditions except the first 0.5 mA condition, and no differences in response between the four current intensities. Cluster analysis identified two clusters for the 0.2 and 2 mA conditions only. Frequency distributions based on individual subject responses (excitatory, inhibitory or no response) to each condition indicate possible differential responses between individuals to different current intensities. Test-retest reliability was negligible (ICC(2,1) = -0.50). Significant inter-individual variability in response to tDCS across a range of current intensities was found. 2 mA and 0.2 mA tDCS were most effective at inducing a distinct response. Significant intra-individual variability in response to tDCS was also found. This has implications for interpreting results of single-session tDCS experiments. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  1. The Harm Done to Reproducibility by the Culture of Null Hypothesis Significance Testing.

    PubMed

    Lash, Timothy L

    2017-09-15

    In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated. In addition, the culture of null hypothesis significance testing discourages quantitative adjustments to account for systematic errors and quantitative incorporation of prior information. These strategies would otherwise improve reproducibility and have not been previously proposed in the widely cited literature on this topic. Without discarding the culture of null hypothesis significance testing and implementing these alternative methods for statistical analysis and inference, all other strategies for improving reproducibility will yield marginal gains at best. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp; Yokokawa, Takumi; Endo, Yuriko

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modestmore » hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet

  3. Metagenomic analysis reveals significant changes of microbial compositions and protective functions during drinking water treatment.

    PubMed

    Chao, Yuanqing; Ma, Liping; Yang, Ying; Ju, Feng; Zhang, Xu-Xiang; Wu, Wei-Min; Zhang, Tong

    2013-12-19

    The metagenomic approach was applied to characterize variations of microbial structure and functions in raw (RW) and treated water (TW) in a drinking water treatment plant (DWTP) at Pearl River Delta, China. Microbial structure was significantly influenced by the treatment processes, shifting from Gammaproteobacteria and Betaproteobacteria in RW to Alphaproteobacteria in TW. Further functional analysis indicated the basic metabolic functions of microorganisms in TW did not vary considerably. However, protective functions, i.e. glutathione synthesis genes in 'oxidative stress' and 'detoxification' subsystems, significantly increased, revealing the surviving bacteria may have higher chlorine resistance. Similar results were also found in glutathione metabolism pathway, which identified the major reaction for glutathione synthesis and supported more genes for glutathione metabolism existed in TW. This metagenomic study largely enhanced our knowledge about the influences of treatment processes, especially chlorination, on bacterial community structure and protective functions (e.g. glutathione metabolism) in ecosystems of DWTPs.

  4. Utility of the T-SPOT®.TB test's borderline category to increase test resolution for results around the cut-off point.

    PubMed

    Rego, Karen; Pereira, Kristen; MacDougall, James; Cruikshank, William

    2018-01-01

    Accurate identification of individuals with TB infection, is required to achieve the WHO's End TB Strategy goals. While there is general acceptance that the T-SPOT.TB test borderline category provides an opportunity to increase test resolution of results around the test cut-off point, this has not been investigated. 645,947 tests were analyzed to determine frequency of borderline results, effect of age and time between tests and associations between subjects' clinical risk factors and retest results. 645,947 tests produced 93.5% negatives, 4% positives, 0.6% invalids, and 1.8% borderlines. Within the borderline results, 5044 were repeated, with 59.2%, 20.0% and 20.2% resolving to negative, positive and borderline, respectively. Age of subject did not affect retest results; however, time between tests indicated that retest resolution occurred with greatest frequency after 90 days. TB risk factors were provided for 2640 subjects and 17% of low risk subjects with a high initial borderline resolved to negative while 27.6% of subjects with high risk and an initial low borderline resolved to positive, suggesting that these subjects could have been inappropriately classified if using a single cut-off point test with no borderline category. This study demonstrates the utility of the T-SPOT.TB test's borderline category to increase test resolution around the test cut-off point. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Coexistence of the 677C>T and 1298A>C MTHFR polymorphisms and its significance in the population of Polish women.

    PubMed

    Wolski, Hubert; Kocięcka, Maria; Mrozikiewicz, Aleksandra E; Barlik, Magdalena; Kurzawińska, Grażyna

    2015-10-01

    The aim of the study was to evaluate the frequency of the 677C>T and 1298A>C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, as well as the coexistence of both these genetic variants in women from the Polish population. A total of 662 women from the Polish population were enrolled in the study group. The frequency of the investigated genotypes of the 677C>T and 1298A>C polymorphisms of the MTHFR gene was analyzed with the use of PCR/RFLP methods. The frequency of the 677CC, 677CT and 677TT genotypes in the studied population of women was 50.60%, 39.88% and 9.52%, respectively As to the 1298AA, 1298AC and 1298CC genotypes, the obtained results were as follows: 42.75%, 47.88% and 9.37%, respectively (Tables II and III). Simultaneous analysis revealed the most frequent coexistence of 677CC/1298AC (28.85%), 677CT/1298AA (20.85%) and 677CT/1298AC (19.03%) genotypes. The coexistence of 677CC/1298AA (12.39%), 677CC/1298CC (9.37%) and 677TT/1298AA (9.51%) genotypes was observed less frequently In the studied population of Polish women, the coexistence of 677CT/1298CC, 677TT/1298AC and 677TT/1298CC genotypes has been not observed. The frequency and coexistence of genotypes of the 677C>T and 1298A>C MTHFR gene polymorphisms in the studied population of Polish women is similar to other North-European populations. Women carriers of the mutated variants of both, 677C>T and 1298A>C polymorphisms of the MTHFR gene should receive special perinatal care in order to prevent fetal defects and thrombosis-related complications during pregnancy It is vital to emphasize the significance of proper education of folate supplementation, especially in pregnant patients and women of reproductive age.

  6. Anodal transcranial direct current stimulation of the right anterior temporal lobe did not significantly affect verbal insight

    PubMed Central

    Ogawa, Takeshi; Shimokawa, Takeaki; Yamashita, Okito

    2017-01-01

    Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight. PMID:28902872

  7. Anodal transcranial direct current stimulation of the right anterior temporal lobe did not significantly affect verbal insight.

    PubMed

    Aihara, Takatsugu; Ogawa, Takeshi; Shimokawa, Takeaki; Yamashita, Okito

    2017-01-01

    Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight.

  8. Many tests of significance: new methods for controlling type I errors.

    PubMed

    Keselman, H J; Miller, Charles W; Holland, Burt

    2011-12-01

    There have been many discussions of how Type I errors should be controlled when many hypotheses are tested (e.g., all possible comparisons of means, correlations, proportions, the coefficients in hierarchical models, etc.). By and large, researchers have adopted familywise (FWER) control, though this practice certainly is not universal. Familywise control is intended to deal with the multiplicity issue of computing many tests of significance, yet such control is conservative--that is, less powerful--compared to per test/hypothesis control. The purpose of our article is to introduce the readership, particularly those readers familiar with issues related to controlling Type I errors when many tests of significance are computed, to newer methods that provide protection from the effects of multiple testing, yet are more powerful than familywise controlling methods. Specifically, we introduce a number of procedures that control the k-FWER. These methods--say, 2-FWER instead of 1-FWER (i.e., FWER)--are equivalent to specifying that the probability of 2 or more false rejections is controlled at .05, whereas FWER controls the probability of any (i.e., 1 or more) false rejections at .05. 2-FWER implicitly tolerates 1 false rejection and makes no explicit attempt to control the probability of its occurrence, unlike FWER, which tolerates no false rejections at all. More generally, k-FWER tolerates k - 1 false rejections, but controls the probability of k or more false rejections at α =.05. We demonstrate with two published data sets how more hypotheses can be rejected with k-FWER methods compared to FWER control.

  9. Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism.

    PubMed

    Domínguez Jiménez, José Luis; Fernández Suárez, Antonio; Muñoz Colmenero, Aurora Úrsula; Fatela Cantillo, Daniel; López Pelayo, Iratxe

    2017-04-01

    There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  10. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

    PubMed

    Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

    2018-01-01

    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

  11. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML

    PubMed Central

    Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D.; Salmena, Leonardo

    2018-01-01

    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher’s exact P values). In our study, Fisher’s exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B’s prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene. PMID:29415082

  12. MRI T2 Mapping of the Knee Articular Cartilage Using Different Acquisition Sequences and Calculation Methods at 1.5 Tesla.

    PubMed

    Mars, Mokhtar; Bouaziz, Mouna; Tbini, Zeineb; Ladeb, Fethi; Gharbi, Souha

    2018-06-12

    This study aims to determine how Magnetic Resonance Imaging (MRI) acquisition techniques and calculation methods affect T2 values of knee cartilage at 1.5 Tesla and to identify sequences that can be used for high-resolution T2 mapping in short scanning times. This study was performed on phantom and twenty-nine patients who underwent MRI of the knee joint at 1.5 Tesla. The protocol includes T2 mapping sequences based on Single Echo Spin Echo (SESE), Multi-Echo Spin Echo (MESE), Fast Spin Echo (FSE) and Turbo Gradient Spin Echo (TGSE). The T2 relaxation times were quantified and evaluated using three calculation methods (MapIt, Syngo Offline and monoexponential fit). Signal to Noise Ratios (SNR) were measured in all sequences. All statistical analyses were performed using the t-test. The average T2 values in phantom were 41.7 ± 13.8 ms for SESE, 43.2 ± 14.4 ms for MESE, 42.4 ± 14.1 ms for FSE and 44 ± 14.5 ms for TGSE. In the patient study, the mean differences were 6.5 ± 8.2 ms, 7.8 ± 7.6 ms and 8.4 ± 14.2 ms for MESE, FSE and TGSE compared to SESE respectively; these statistical results were not significantly different (p > 0.05). The comparison between the three calculation methods showed no significant difference (p > 0.05). t-Test showed no significant difference between SNR values for all sequences. T2 values depend not only on the sequence type but also on the calculation method. None of the sequences revealed significant differences compared to the SESE reference sequence. TGSE with its short scanning time can be used for high-resolution T2 mapping. ©2018The Author(s). Published by S. Karger AG, Basel.

  13. Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4+ T Cells in Peripheral Blood of Subjects with Type 1 Diabetes.

    PubMed

    Cerosaletti, Karen; Barahmand-Pour-Whitman, Fariba; Yang, Junbao; DeBerg, Hannah A; Dufort, Matthew J; Murray, Sara A; Israelsson, Elisabeth; Speake, Cate; Gersuk, Vivian H; Eddy, James A; Reijonen, Helena; Greenbaum, Carla J; Kwok, William W; Wambre, Erik; Prlic, Martin; Gottardo, Raphael; Nepom, Gerald T; Linsley, Peter S

    2017-07-01

    The significance of islet Ag-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects is unclear, partly because similar cells are also found in healthy control (HC) subjects. We hypothesized that key disease-associated cells would show evidence of prior Ag exposure, inferred from expanded TCR clonotypes, and essential phenotypic properties in their transcriptomes. To test this, we developed single-cell RNA sequencing procedures for identifying TCR clonotypes and transcript phenotypes in individual T cells. We applied these procedures to analysis of islet Ag-reactive CD4 + memory T cells from the blood of T1D and HC individuals after activation with pooled immunodominant islet peptides. We found extensive TCR clonotype sharing in Ag-activated cells, especially from individual T1D subjects, consistent with in vivo T cell expansion during disease progression. The expanded clonotype from one T1D subject was detected at repeat visits spanning >15 mo, demonstrating clonotype stability. Notably, we found no clonotype sharing between subjects, indicating a predominance of "private" TCR specificities. Expanded clones from two T1D subjects recognized distinct IGRP peptides, implicating this molecule as a trigger for CD4 + T cell expansion. Although overall transcript profiles of cells from HC and T1D subjects were similar, profiles from the most expanded clones were distinctive. Our findings demonstrate that islet Ag-reactive CD4 + memory T cells with unique Ag specificities and phenotypes are expanded during disease progression and can be detected by single-cell analysis of peripheral blood. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Significance of Iron(II,III) Hydroxycarbonate Green Rust in Arsenic Remediation Using Zerovalent Iron in Laboratory Column Tests

    EPA Science Inventory

    We examined the corrosion products of zerovalent iron used in three column tests for removing arsenic from water under dynamic flow conditions. Each column test lasted three- to four-months using columns consisting of a 10.3-cm depth of 50 : 50 (w : w, Peerless iron : sand) in t...

  15. Type 1 diabetes mellitus effects on dental enamel formation revealed by microscopy and microanalysis.

    PubMed

    Silva, Bruna Larissa Lago; Medeiros, Danila Lima; Soares, Ana Prates; Line, Sérgio Roberto Peres; Pinto, Maria das Graças Farias; Soares, Telma de Jesus; do Espírito Santo, Alexandre Ribeiro

    2018-03-01

    Type 1 diabetes mellitus (T1DM) largely affects children, occurring therefore at the same period of deciduous and permanent teeth development. The aim of this work was to investigate birefringence and morphology of the secretory stage enamel organic extracellular matrix (EOECM), and structural and mechanical features of mature enamel from T1DM rats. Adult Wistar rats were maintained alive for a period of 56 days after the induction of experimental T1DM with a single dose of streptozotocin (60 mg/kg). After proper euthanasia of the animals, fixed upper incisors were accurately processed, and secretory stage EOECM and mature enamel were analyzed by transmitted polarizing and bright field light microscopies (TPLM and BFLM), energy-dispersive x-ray (EDX) analysis, scanning electron microscopy (SEM), and microhardness testing. Bright field light microscopies and transmitted polarizing light microscopies showed slight morphological changes in the secretory stage EOECM from diabetic rats, which also did not exhibit statistically significant alterations in birefringence brightness when compared to control animals (P > .05). EDX analysis showed that T1DM induced statistically significant little increases in the amount of calcium and phosphorus in outer mature enamel (P < .01) with preservation of calcium/phosphorus ratio in that structure (P > .05). T1DM also caused important ultrastructural alterations in mature enamel as revealed by SEM and induced a statistically significant reduction of about 13.67% in its microhardness at 80 μm from dentin-enamel junction (P < .01). This study shows that T1DM may disturb enamel development, leading to alterations in mature enamel ultrastructure and in its mechanical features. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals

    PubMed Central

    Musharraf, Syed Ghulam; Iqbal, Ayesha; Ansari, Saqib Hussain; Parveen, Sadia; Khan, Ishtiaq Ahmad; Siddiqui, Amna Jabbar

    2017-01-01

    β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals. PMID:28198811

  17. A Pattern of Perseveration in Cocaine Addiction May Reveal Neurocognitive Processes Implicit in the Wisconsin Card Sorting Test

    PubMed Central

    Woicik, Patricia A.; Urban, Catherine; Alia-Klein, Nelly; Henry, Ashley; Maloney, Thomas; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

    2011-01-01

    The ability to adapt behavior in a changing environment is necessary for humans to achieve their goals and can be measured in the lab with tests of rule-based switching. Disease models, such as cocaine addiction, have revealed that alterations in dopamine interfere with adaptive set switching, culminating in perseveration. We explore perseverative behavior in individuals with cocaine use disorders (CUD) and healthy controls (CON) during performance of the Wisconsin Card Sorting Test (WCST) (N = 107 in each group). By examining perseverative errors within each of the 6 blocks of the WCST, we uniquely test two forms of set switching that are differentiated by either the presence (extradimensional set shifting (EDS) – first 3 blocks) or absence (task-set switching – last 3 blocks) of contingency learning. We also explore relationships between perseveration and select cognitive and drug use factors including verbal learning and memory, trait inhibitory control, motivational state, and urine status for cocaine (in CUD). Results indicate greater impairment for CUD than CON on the WCST, even in higher performing CUD who completed all 6 blocks of the WCST. Block by block analysis conducted on completers’ scores indicate a tendency for greater perseveration in CUD than CON but only during the first task-set switch; no such deficits were observed during EDS. This task-set switching impairment was modestly associated with two indices of immediate recall (r = −.32, −.29) and urine status for cocaine [t (134) = 2.3, p <.03]. By distinguishing these two forms of switching on the WCST, the current study reveals a neurocognitive context (i.e. initial stage of task-set switching) implicit in the WCST that possibly relies upon intact dopaminergic function, but that is impaired in CUD, as associated with worse recall and possibly withdrawal from cocaine. Future studies should investigate whether dopaminergically innervated pathways alone, or in combination with other

  18. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids

    PubMed Central

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M.; Söll, Dieter

    2015-01-01

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNAPyl to create tRNAPyl-opt with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (Nϵ-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNAPyl-opt facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNAPyl-opt with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNAPyl-opt had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNAPyl-opt should be an excellent replacement of wild-type tRNAPyl for future ncAA incorporation by PylRS enzymes. PMID:26250114

  19. Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

    PubMed

    Yilmaz, Meral; Tas, Ayca; Donmez, Gonca; Kacan, Turgut; Silig, Yavuz

    2018-04-27

    Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population. Creative Commons Attribution License

  20. Urushiol Patch Test Using the T.R.U.E. TEST System.

    PubMed

    Kim, Yesul; Longenecker, Amy; ElSohly, Mahmoud A; Gul, Waseem; Hage, Raymond J; Hamann, Curtis P; Marks, James G

    Poison ivy, poison oak, and poison sumac are the most common causes of allergic contact dermatitis in North America. Although extensive efforts have been made to develop therapies that prevent and treat allergic contact dermatitis to these plants, there lacks an entirely effective method, besides complete avoidance. Efforts to develop a more effective preventive therapy, such as a vaccine, are ongoing. To accurately evaluate the efficacy of these new therapies, an appropriate assessment tool is needed. The aim of this study was to evaluate the safety and appropriate doses of urushiol required for a patch test based on the hydrogel delivery system of the Thin-Layer Rapid Use Epicutaneous Patch Test. Nine subjects were patch tested with various doses of urushiol and a negative control on day 0. Patch test sites were inspected for any local reaction on days 2, 4, 7, 14, and 21 after the initial exposure and graded by standard morphology. All 9 subjects did not have any significant adverse effects. The urushiol patch test using the hydrogel delivery method demonstrated urushiol sensitivity. All doses of urushiol resulted in a local reaction, and severity of reactions was correlated with dosage of urushiol used in the patch test.

  1. Co-Educational Tutorial Classes and Their Significance on Gendered Test Scores of Wollo University Students: A Before-After Analyses

    ERIC Educational Resources Information Center

    Gidey, Mu'uz

    2015-01-01

    This action research is carried out in a practical class room setting to devise an innovative way of administering tutorial classes to improve students' learning competence with particular reference to gendered test scores. A before-after test score analyses of mean and standard deviations along with t-statistical tests of hypotheses of second…

  2. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance

    PubMed Central

    Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

    2015-01-01

    A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

  3. 40 CFR Appendix IV to Part 264 - Cochran's Approximation to the Behrens-Fisher Students' t-test

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... summary measures to calculate a t-statistic (t*) and a comparison t-statistic (tc). The t* value is compared to the tc value and a conclusion reached as to whether there has been a statistically significant... made in collecting the background data. The t-statistic (tc), against which t* will be compared...

  4. 40 CFR Appendix IV to Part 264 - Cochran's Approximation to the Behrens-Fisher Students' t-test

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... summary measures to calculate a t-statistic (t*) and a comparison t-statistic (tc). The t* value is compared to the tc value and a conclusion reached as to whether there has been a statistically significant... made in collecting the background data. The t-statistic (tc), against which t* will be compared...

  5. "I Don't Know" and Multiple Choice Analysis of Pre- and Post-Tests

    ERIC Educational Resources Information Center

    Spears, Karen; Wilson, Mary

    2010-01-01

    Evaluation is an essential component of any Extension education program. One tool, the pre- and post-test, provides measurable evaluation data. Yet often the answer "I don't know" or all possible answers to a multiple choice question are not included in the repeated measure analysis. Because more than two answers are offered, the test of marginal…

  6. Cumulative effects of anodal and priming cathodal tDCS on pegboard test performance and motor cortical excitability.

    PubMed

    Christova, Monica; Rafolt, Dietmar; Gallasch, Eugen

    2015-01-01

    Transcranial direct current stimulation (tDCS) protocols applied over the primary motor cortex are associated with changes in motor performance. This transcranial magnetic stimulation (TMS) study examines whether cathodal tDCS prior to motor training, combined with anodal tDCS during motor training improves motor performance and off-line learning. Three study groups (n=36) were trained on the grooved pegboard test (GPT) in a randomized, between-subjects design: SHAM-sham stimulation prior and during training, STIM1-sham stimulation prior and atDCS during training, STIM2-ctDCS stimulation prior and atDCS during training. Motor performance was assessed by GPT completion time and retested 14 days later to determine off-line learning. Cortical excitability was assessed via TMS at baseline (T0), prior training (T1), after training (T2), and 60 min after training (T3). Motor evoked potentials (MEP) were recorded from m. abductor pollicis brevis of the active left hand. GPT completion time was reduced for both stimulated groups compared to SHAM. For STIM2 this reduction in time was significantly higher than for STIM1 and further off-line learning occurred after STIM2. After ctDCS at T1, MEP amplitude and intracortical facilitation was decreased and intracortical inhibition was increased. After atDCS at T2, an opposite effect was observed for STIM1 and STIM2. For STIM2 these neuromodulatory effects were retained until T3. It is concluded that application of atDCS during the training improves pegboard performance and that additional priming with ctDCS has a positive effect on off-line learning. These cumulative behavioral gains were indicated by the preceding neuromodulatory changes. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Expression of Master Regulators of T-cell, Helper T-cell and Follicular Helper T-cell Differentiation in Angioimmunoblastic T-cell Lymphoma.

    PubMed

    Matsumoto, Yosuke; Nagoshi, Hisao; Yoshida, Mihoko; Kato, Seiichi; Kuroda, Junya; Shimura, Kazuho; Kaneko, Hiroto; Horiike, Shigeo; Nakamura, Shigeo; Taniwaki, Masafumi

    2017-11-01

    Objective It has been postulated that the normal counterpart of angioimmunoblastic T-cell lymphoma (AITL) is the follicular helper T-cell (TFH). Recent immunological studies have identified several transcription factors responsible for T-cell differentiation. The master regulators associated with T-cell, helper T-cell (Th), and TFH differentiation are reportedly BCL11B, Th-POK, and BCL6, respectively. We explored the postulated normal counterpart of AITL with respect to the expression of the master regulators of T-cell differentiation. Methods We performed an immunohistochemical analysis in 15 AITL patients to determine the expression of the master regulators and several surface markers associated with T-cell differentiation. Results BCL11B was detected in 10 patients (67%), and the surface marker of T-cells (CD3) was detected in all patients. Only 2 patients (13%) expressed the marker of naïve T-cells (CD45RA), but all patients expressed the marker of effector T-cells (CD45RO). Nine patients expressed Th-POK (60%), and 7 (47%) expressed a set of surface antigens of Th (CD4-positive and CD8-negative). In addition, BCL6 and the surface markers of TFH (CXCL13, PD-1, and SAP) were detected in 11 (73%), 8 (53%), 14 (93%), and all patients, respectively. Th-POK-positive/BCL6-negative patients showed a significantly shorter overall survival (OS) than the other patients (median OS: 33.0 months vs. 74.0 months, p=0.020; log-rank test). Conclusion Many of the AITL patients analyzed in this study expressed the master regulators of T-cell differentiation. The clarification of the diagnostic significance and pathophysiology based on the expression of these master regulators in AITL is expected in the future.

  8. "What If" Analyses: Ways to Interpret Statistical Significance Test Results Using EXCEL or "R"

    ERIC Educational Resources Information Center

    Ozturk, Elif

    2012-01-01

    The present paper aims to review two motivations to conduct "what if" analyses using Excel and "R" to understand the statistical significance tests through the sample size context. "What if" analyses can be used to teach students what statistical significance tests really do and in applied research either prospectively to estimate what sample size…

  9. Interpretation and classification of microvolt T wave alternans tests

    NASA Technical Reports Server (NTRS)

    Bloomfield, Daniel M.; Hohnloser, Stefan H.; Cohen, Richard J.

    2002-01-01

    Measurement of microvolt-level T wave alternans (TWA) during routine exercise stress testing now is possible as a result of sophisticated noise reduction techniques and analytic methods that have become commercially available. Even though this technology is new, the available data suggest that microvolt TWA is a potent predictor of arrhythmia risk in diverse disease states. As this technology becomes more widely available, physicians will be called upon to interpret microvolt TWA tracings. This review seeks to establish uniform standards for the clinical interpretation of microvolt TWA tracings.

  10. Elevated phenylalanine on newborn screening: follow-up testing may reveal undiagnosed galactosaemia.

    PubMed

    Shakespeare, Lynette; Downing, Melanie; Allen, Joyce; Casbolt, Ann-Marie; Ellin, Sheila; Maloney, Martin; Race, Gillian; Bonham, Jim

    2010-11-01

    Introduction Newborn screening for phenylketonuria (PKU) can reveal other conditions which lead to an increased blood spot phenylalanine (Phe) concentration. We have investigated the proportion of blood spot samples that gave a positive screen due to clinically significant conditions other than PKU, compared the positive predictive value (PPV) of our referral Phe cut-off with that recommended by the UK Newborn Screening Programme Centre (UKNSPC) (>210 and >240 μmol/L, respectively) and evaluated the effectiveness of reflex testing for galactosaemia using a lower blood spot Phe cut-off concentration of 130 μmol/L. All blood spot samples that screened positive, for an increased Phe concentration, between April 2001 and March 2008, were identified from the records of the Sheffield Newborn Screening Laboratory and the diagnoses noted. In addition, all cases of galactosaemia detected in or notified to our screening laboratory within this time were also examined and the screened Phe concentrations compared. Out of 438,674 babies who were screened, 67 had Phe concentration >210 μmol/L (15 per 100,000). Of these, 40 had PKU or persistent hyperphenylalaninaemia with a Phe concentration identified by screening between 270 and 2350 μmol/L. A further 11 were diagnosed with another clinically significant disorder: galactosaemia (n = 8), biopterin defects (n = 2), tyrosinaemia Type 1 (n = 1). In addition, 16 had transient elevations in Phe. In total, nine cases of galactosaemia were identified, of whom, three had Phe concentrations <240 μmol/L with one asymptomatic individual having a concentration <210 μmol/L. Adoption of the UKNSPC recommended cut-off (>240 μmol/L) will not affect the detection rate of classical PKU, but will improve the PPV from 76% to 80%. The use of a lower cut-off (130 μmol/L) for reflex galactosaemia testing enables the timely identification of asymptomatic cases that benefit particularly from early treatment, without prompting any unnecessary

  11. MASH test 3-11 of the TxDOT T222 bridge rail.

    DOT National Transportation Integrated Search

    2016-07-01

    The objective of this research was to evaluate the impact performance of the TxDOT Type T222 : Bridge Rail according to the Manual for Assessing Safety Hardware (MASH) TL-3. The crash testing was : performed in accordance with the requirements of MAS...

  12. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation

    PubMed Central

    Martinez, Emily M.; Yoshida, Miya C.; Candelario, Tara Lynne T.

    2015-01-01

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

  13. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

    PubMed

    Martinez, Emily M; Yoshida, Miya C; Candelario, Tara Lynne T; Hughes-Fulford, Millie

    2015-03-15

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.

  14. Using the Descriptive Bootstrap to Evaluate Result Replicability (Because Statistical Significance Doesn't)

    ERIC Educational Resources Information Center

    Spinella, Sarah

    2011-01-01

    As result replicability is essential to science and difficult to achieve through external replicability, the present paper notes the insufficiency of null hypothesis statistical significance testing (NHSST) and explains the bootstrap as a plausible alternative, with a heuristic example to illustrate the bootstrap method. The bootstrap relies on…

  15. Serotyping of Toxoplasma gondii in Cats (Felis domesticus) Reveals Predominance of Type II Infections in Germany

    PubMed Central

    Maksimov, Pavlo; Zerweck, Johannes; Dubey, Jitender P.; Pantchev, Nikola; Frey, Caroline F.; Maksimov, Aline; Reimer, Ulf; Schutkowski, Mike; Hosseininejad, Morteza; Ziller, Mario; Conraths, Franz J.; Schares, Gereon

    2013-01-01

    Background Cats are definitive hosts of Toxoplasma gondii and play an essential role in the epidemiology of this parasite. The study aims at clarifying whether cats are able to develop specific antibodies against different clonal types of T. gondii and to determine by serotyping the T. gondii clonal types prevailing in cats as intermediate hosts in Germany. Methodology To establish a peptide-microarray serotyping test, we identified 24 suitable peptides using serological T. gondii positive (n=21) and negative cat sera (n=52). To determine the clonal type-specific antibody response of cats in Germany, 86 field sera from T. gondii seropositive naturally infected cats were tested. In addition, we analyzed the antibody response in cats experimentally infected with non-canonical T. gondii types (n=7). Findings Positive cat reference sera reacted predominantly with peptides harbouring amino acid sequences specific for the clonal T. gondii type the cats were infected with. When the array was applied to field sera from Germany, 98.8% (85/86) of naturally-infected cats recognized similar peptide patterns as T. gondii type II reference sera and showed the strongest reaction intensities with clonal type II-specific peptides. In addition, naturally infected cats recognized type II-specific peptides significantly more frequently than peptides of other type-specificities. Cats infected with non-canonical types showed the strongest reactivity with peptides presenting amino-acid sequences specific for both, type I and type III. Conclusions Cats are able to mount a clonal type-specific antibody response against T. gondii. Serotyping revealed for most seropositive field sera patterns resembling those observed after clonal type II-T. gondii infection. This finding is in accord with our previous results on the occurrence of T. gondii clonal types in oocysts shed by cats in Germany. PMID:24244652

  16. Face Perception and Test Reliabilities in Congenital Prosopagnosia in Seven Tests

    PubMed Central

    Esins, Janina; Schultz, Johannes; Stemper, Claudia; Kennerknecht, Ingo

    2016-01-01

    Congenital prosopagnosia, the innate impairment in recognizing faces, is a very heterogeneous disorder with different phenotypical manifestations. To investigate the nature of prosopagnosia in more detail, we tested 16 prosopagnosics and 21 controls with an extended test battery addressing various aspects of face recognition. Our results show that prosopagnosics exhibited significant impairments in several face recognition tasks: impaired holistic processing (they were tested amongst others with the Cambridge Face Memory Test (CFMT)) as well as reduced processing of configural information of faces. This test battery also revealed some new findings. While controls recognized moving faces better than static faces, prosopagnosics did not exhibit this effect. Furthermore, prosopagnosics had significantly impaired gender recognition—which is shown on a groupwise level for the first time in our study. There was no difference between groups in the automatic extraction of face identity information or in object recognition as tested with the Cambridge Car Memory Test. In addition, a methodological analysis of the tests revealed reduced reliability for holistic face processing tests in prosopagnosics. To our knowledge, this is the first study to show that prosopagnosics showed a significantly reduced reliability coefficient (Cronbach’s alpha) in the CFMT compared to the controls. We suggest that compensatory strategies employed by the prosopagnosics might be the cause for the vast variety of response patterns revealed by the reduced test reliability. This finding raises the question whether classical face tests measure the same perceptual processes in controls and prosopagnosics. PMID:27482369

  17. Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

    PubMed Central

    Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

    2014-01-01

    Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

  18. Testing the scalar expectancy theory (SET) and the learning-to-time model (LeT) in a double bisection task.

    PubMed

    Machado, Armando; Pata, Paulo

    2005-02-01

    Two theories of timing, scalar expectancy theory (SET) and learning-to-time (LeT), make substantially different assumptions about what animals learn in temporal tasks. In a test of these assumptions, pigeons learned two temporal discriminations. On Type 1 trials, they learned to choose a red key after a 1-sec signal and a green key after a 4-sec signal; on Type 2 trials, they learned to choose a blue key after a 4-sec signal and a yellow key after either an 8-sec signal (Group 8) or a 16-sec signal (Group 16). Then, the birds were exposed to signals 1 sec, 4 sec, and 16 sec in length and given a choice between novel key combinations (red or green vs. blue or yellow). The choice between the green key and the blue key was of particular significance because both keys were associated with the same 4-sec signal. Whereas SET predicted no effect of the test signal duration on choice, LeT predicted that preference for green would increase monotonically with the length of the signal but would do so faster for Group 8 than for Group 16. The results were consistent with LeT, but not with SET.

  19. Polymorphism of Cyp1a1 (T6235C) is not a significant risk factor of osteoporosis in postmenopausal Indonesian woman

    NASA Astrophysics Data System (ADS)

    Auerkari, EI; Budhy, LW; Kiranahayu, R.; Djamal, NZ; Kusdhany, LS; Rahardjo, TBW; Talbot, Christopher

    2018-05-01

    Osteoporosis is an increasingly common disease resulting in reduced bone mineral density (BMD) and elevated likelihood of bone fracture, and particularly affected are postmenopausal women with additional risk factors including genetic predisposition. The CYP1A1, is one of the candidate genes that have been suggested to be associated with the pathogenesis of osteoporosis. This work aimed to evaluate the distribution of a selected polymorphism of this gene (T6235C) with respect to the BMD status in postmenopausal Indonesian women. The results show that osteoporosis is associated with age and menopause, as expected, but not with the tested polymorphism of CYP1A1 in the Indonesian sample population. It is suggested that other P450 cytochrome enzymes and their polymorphisms could provide more significant indicators of the future health of postmenopausal women.

  20. Training Materials and Data Requirements for Turret Organizational Maintenance Trainer (TOM-T) Training Test Support Plan

    DTIC Science & Technology

    1980-05-01

    performed on the TOM-T Turret Mock- Up . Those marked with a number symbol (#) can be done on the TOM-T Programmable Maintenance Trainer. Tasks with both...an asterisk and a number symbol (*/#) are those which can be performed partially on the turret mock- up and partially on the programmable trainer...time, the tasks serve as prerequisites to troubleshooting. With the exception of setting- up , testing, and shutting-down the STE/XMI test set, and

  1. Monte Carlo Simulations Comparing Fisher Exact Test and Unequal Variances t Test for Analysis of Differences Between Groups in Brief Hospital Lengths of Stay.

    PubMed

    Dexter, Franklin; Bayman, Emine O; Dexter, Elisabeth U

    2017-12-01

    We examined type I and II error rates for analysis of (1) mean hospital length of stay (LOS) versus (2) percentage of hospital LOS that are overnight. These 2 end points are suitable for when LOS is treated as a secondary economic end point. We repeatedly resampled LOS for 5052 discharges of thoracoscopic wedge resections and lung lobectomy at 26 hospitals. Unequal variances t test (Welch method) and Fisher exact test both were conservative (ie, type I error rate less than nominal level). The Wilcoxon rank sum test was included as a comparator; the type I error rates did not differ from the nominal level of 0.05 or 0.01. Fisher exact test was more powerful than the unequal variances t test at detecting differences among hospitals; estimated odds ratio for obtaining P < .05 with Fisher exact test versus unequal variances t test = 1.94, with 95% confidence interval, 1.31-3.01. Fisher exact test and Wilcoxon-Mann-Whitney had comparable statistical power in terms of differentiating LOS between hospitals. For studies with LOS to be used as a secondary end point of economic interest, there is currently considerable interest in the planned analysis being for the percentage of patients suitable for ambulatory surgery (ie, hospital LOS equals 0 or 1 midnight). Our results show that there need not be a loss of statistical power when groups are compared using this binary end point, as compared with either Welch method or Wilcoxon rank sum test.

  2. Hydrogen–Deuterium Exchange and Mass Spectrometry Reveal the pH-Dependent Conformational Changes of Diphtheria Toxin T Domain

    PubMed Central

    2015-01-01

    The translocation (T) domain of diphtheria toxin plays a critical role in moving the catalytic domain across the endosomal membrane. Translocation/insertion is triggered by a decrease in pH in the endosome where conformational changes of T domain occur through several kinetic intermediates to yield a final trans-membrane form. High-resolution structural studies are only applicable to the static T-domain structure at physiological pH, and studies of the T-domain translocation pathway are hindered by the simultaneous presence of multiple conformations. Here, we report the application of hydrogen–deuterium exchange mass spectrometry (HDX-MS) for the study of the pH-dependent conformational changes of the T domain in solution. Effects of pH on intrinsic HDX rates were deconvolved by converting the on-exchange times at low pH into times under our “standard condition” (pH 7.5). pH-Dependent HDX kinetic analysis of T domain clearly reveals the conformational transition from the native state (W-state) to a membrane-competent state (W+-state). The initial transition occurs at pH 6 and includes the destabilization of N-terminal helices accompanied by the separation between N- and C-terminal segments. The structural rearrangements accompanying the formation of the membrane-competent state expose a hydrophobic hairpin (TH8–9) to solvent, prepare it to insert into the membrane. At pH 5.5, the transition is complete, and the protein further unfolds, resulting in the exposure of its C-terminal hydrophobic TH8–9, leading to subsequent aggregation in the absence of membranes. This solution-based study complements high resolution crystal structures and provides a detailed understanding of the pH-dependent structural rearrangement and acid-induced oligomerization of T domain. PMID:25290210

  3. Hydrogen-deuterium exchange and mass spectrometry reveal the pH-dependent conformational changes of diphtheria toxin T domain.

    PubMed

    Li, Jing; Rodnin, Mykola V; Ladokhin, Alexey S; Gross, Michael L

    2014-11-04

    The translocation (T) domain of diphtheria toxin plays a critical role in moving the catalytic domain across the endosomal membrane. Translocation/insertion is triggered by a decrease in pH in the endosome where conformational changes of T domain occur through several kinetic intermediates to yield a final trans-membrane form. High-resolution structural studies are only applicable to the static T-domain structure at physiological pH, and studies of the T-domain translocation pathway are hindered by the simultaneous presence of multiple conformations. Here, we report the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) for the study of the pH-dependent conformational changes of the T domain in solution. Effects of pH on intrinsic HDX rates were deconvolved by converting the on-exchange times at low pH into times under our "standard condition" (pH 7.5). pH-Dependent HDX kinetic analysis of T domain clearly reveals the conformational transition from the native state (W-state) to a membrane-competent state (W(+)-state). The initial transition occurs at pH 6 and includes the destabilization of N-terminal helices accompanied by the separation between N- and C-terminal segments. The structural rearrangements accompanying the formation of the membrane-competent state expose a hydrophobic hairpin (TH8-9) to solvent, prepare it to insert into the membrane. At pH 5.5, the transition is complete, and the protein further unfolds, resulting in the exposure of its C-terminal hydrophobic TH8-9, leading to subsequent aggregation in the absence of membranes. This solution-based study complements high resolution crystal structures and provides a detailed understanding of the pH-dependent structural rearrangement and acid-induced oligomerization of T domain.

  4. Multi-omics Reveals the Lifestyle of the Acidophilic, Mineral-Oxidizing Model Species Leptospirillum ferriphilumT

    PubMed Central

    2017-01-01

    ABSTRACT Leptospirillum ferriphilum plays a major role in acidic, metal-rich environments, where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of the type strain of this model species is available, limiting the possibilities to investigate the strategies and adaptations that Leptospirillum ferriphilum DSM 14647T (here referred to as Leptospirillum ferriphilumT) applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilumT obtained by PacBio single-molecule real-time (SMRT) long-read sequencing for use as a high-quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, the oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as the substrate and those grown in bioleaching cultures containing chalcopyrite (CuFeS2). Adaptations of Leptospirillum ferriphilumT to growth on chalcopyrite included the possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated levels of RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, the expression and translation of genes responsible for chemotaxis and motility were enhanced. IMPORTANCE Leptospirillum ferriphilum is one of the most important iron oxidizers in the context of acidic and metal-rich environments during moderately thermophilic biomining. A high-quality circular

  5. Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test.

    PubMed

    Sellers, Kristin K; Mellin, Juliann M; Lustenberger, Caroline M; Boyle, Michael R; Lee, Won Hee; Peterchev, Angel V; Fröhlich, Flavio

    2015-09-01

    Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants were included in the final analysis. These participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2 mA at each anode for 20 min) or active sham tDCS (2 mA for 40 s), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2 mA for 20 min). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Why significant variables aren't automatically good predictors.

    PubMed

    Lo, Adeline; Chernoff, Herman; Zheng, Tian; Lo, Shaw-Hwa

    2015-11-10

    Thus far, genome-wide association studies (GWAS) have been disappointing in the inability of investigators to use the results of identified, statistically significant variants in complex diseases to make predictions useful for personalized medicine. Why are significant variables not leading to good prediction of outcomes? We point out that this problem is prevalent in simple as well as complex data, in the sciences as well as the social sciences. We offer a brief explanation and some statistical insights on why higher significance cannot automatically imply stronger predictivity and illustrate through simulations and a real breast cancer example. We also demonstrate that highly predictive variables do not necessarily appear as highly significant, thus evading the researcher using significance-based methods. We point out that what makes variables good for prediction versus significance depends on different properties of the underlying distributions. If prediction is the goal, we must lay aside significance as the only selection standard. We suggest that progress in prediction requires efforts toward a new research agenda of searching for a novel criterion to retrieve highly predictive variables rather than highly significant variables. We offer an alternative approach that was not designed for significance, the partition retention method, which was very effective predicting on a long-studied breast cancer data set, by reducing the classification error rate from 30% to 8%.

  7. Next-Generation Sequencing Reveals Significant Bacterial Diversity of Botrytized Wine

    PubMed Central

    Bokulich, Nicholas A.; Joseph, C. M. Lucy; Allen, Greg; Benson, Andrew K.; Mills, David A.

    2012-01-01

    While wine fermentation has long been known to involve complex microbial communities, the composition and role of bacteria other than a select set of lactic acid bacteria (LAB) has often been assumed either negligible or detrimental. This study served as a pilot study for using barcoded amplicon next-generation sequencing to profile bacterial community structure in wines and grape musts, comparing the taxonomic depth achieved by sequencing two different domains of prokaryotic 16S rDNA (V4 and V5). This study was designed to serve two goals: 1) to empirically determine the most taxonomically informative 16S rDNA target region for barcoded amplicon sequencing of wine, comparing V4 and V5 domains of bacterial 16S rDNA to terminal restriction fragment length polymorphism (TRFLP) of LAB communities; and 2) to explore the bacterial communities of wine fermentation to better understand the biodiversity of wine at a depth previously unattainable using other techniques. Analysis of amplicons from the V4 and V5 provided similar views of the bacterial communities of botrytized wine fermentations, revealing a broad diversity of low-abundance taxa not traditionally associated with wine, as well as atypical LAB communities initially detected by TRFLP. The V4 domain was determined as the more suitable read for wine ecology studies, as it provided greater taxonomic depth for profiling LAB communities. In addition, targeted enrichment was used to isolate two species of Alphaproteobacteria from a finished fermentation. Significant differences in diversity between inoculated and uninoculated samples suggest that Saccharomyces inoculation exerts selective pressure on bacterial diversity in these fermentations, most notably suppressing abundance of acetic acid bacteria. These results determine the bacterial diversity of botrytized wines to be far higher than previously realized, providing further insight into the fermentation dynamics of these wines, and demonstrate the utility of next

  8. Assessment of statistical significance and clinical relevance.

    PubMed

    Kieser, Meinhard; Friede, Tim; Gondan, Matthias

    2013-05-10

    In drug development, it is well accepted that a successful study will demonstrate not only a statistically significant result but also a clinically relevant effect size. Whereas standard hypothesis tests are used to demonstrate the former, it is less clear how the latter should be established. In the first part of this paper, we consider the responder analysis approach and study the performance of locally optimal rank tests when the outcome distribution is a mixture of responder and non-responder distributions. We find that these tests are quite sensitive to their planning assumptions and have therefore not really any advantage over standard tests such as the t-test and the Wilcoxon-Mann-Whitney test, which perform overall well and can be recommended for applications. In the second part, we present a new approach to the assessment of clinical relevance based on the so-called relative effect (or probabilistic index) and derive appropriate sample size formulae for the design of studies aiming at demonstrating both a statistically significant and clinically relevant effect. Referring to recent studies in multiple sclerosis, we discuss potential issues in the application of this approach. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilumT.

    PubMed

    Christel, Stephan; Herold, Malte; Bellenberg, Sören; El Hajjami, Mohamed; Buetti-Dinh, Antoine; Pivkin, Igor V; Sand, Wolfgang; Wilmes, Paul; Poetsch, Ansgar; Dopson, Mark

    2017-11-17

    Leptospirillum ferriphilum plays a major role in acidic, metal rich environments where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of this model species' type strain is available, limiting the possibilities to investigate the strategies and adaptations Leptospirillum ferriphilum T applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilum T DSM 14647 obtained by PacBio SMRT long read sequencing for use as a high quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as substrate and bioleaching cultures containing chalcopyrite (CuFeS 2 ). Leptospirillum ferriphilum T adaptations to growth on chalcopyrite included a possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, expression and translation of genes responsible for chemotaxis and motility were enhanced. IMPORTANCE Leptospirillum ferriphilum is one of the most important iron-oxidizers in the context of acidic and metal rich environments during moderately thermophilic biomining. A high-quality circular genome of Leptospirillum ferriphilum T coupled with functional omics data provides new insights into its metabolic properties, such as the

  10. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

    PubMed

    Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

    2017-07-01

    HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

  11. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation

    PubMed Central

    Planas, Delphine; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R. M.

    2017-01-01

    HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation. PMID:28727807

  12. Terminally differentiated CD8+ T cells and CD57−FOXP3+CD8+ T cells are highly associated with the efficacy of immunotherapy using activated autologous lymphocytes

    PubMed Central

    Akagi, Junji; Baba, Hideo; Sekine, Teruaki; Ogawa, Kenji

    2018-01-01

    Treatment with activated autologous lymphocytes (AALs) has demonstrated mixed results for cancer treatment. Preliminary results revealed that the proportion of cluster of differentiation (CD)8+CD57+ T cells is significantly increased in AALs, indicating that they are able to determine treatment outcome. Therefore, the role of CD8+CD57+ T cells in AAL efficacy was investigated. T lymphocytes were isolated from 35 patients with stage IV gastric carcinomas (17 men and 18 women; aged 41–84 years) receiving immunotherapy using AALs (IAAL). Using fluorescence activated cell sorting, CD8, CD27, CD57, and forkhead box protein 3 (FOXP3) expression was investigated on CD8+ T cell populations in CD8+ T cell differentiation prior to and following in vitro culture. The association between these populations and progression-free survival (PFS) was analyzed using Cox univariate, and multivariate analyses and Kaplan-Meier survival analysis. CD57 expression was negative in early-differentiated CD8+ T cells (CD27+CD8+CD57−), and positive in intermediate- (CD27+CD8+CD57+) and terminal- (CD27−CD8+CD57+) differentiated CD8+ T cells. Univariate analysis revealed a significant association between terminal-CD8+ T cells and longer PFS times (P=0.035), whereas CD57−FOXP3+CD8+ T cells were associated with shorter PFS times. Multivariate analysis revealed that CD57−FOXP3+CD8+ T cells was an independent poor prognostic factor, whereas CD57+FOXP3+CD8+ T cells were not associated with PFS. Although IAAL increased the proportion of terminal-CD8+ T cells relative to the pre-culture proportions, patients with a high CD57−FOXP3+CD8+ T cell percentage exhibited repressed terminal-CD8+ T cell induction, leading to poor patient prognosis. Terminally differentiated CD27−CD8+CD57+ T cells were responsible for the effectiveness of AALs; however, CD57−FOXP3+CD8+ T cells abrogated their efficacy, possibly by inhibiting their induction.

  13. 26 CFR 1.883-4T - Qualified shareholder stock ownership test (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Qualified shareholder stock ownership test... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Foreign Corporations § 1.883-4T Qualified shareholder stock...)(E) through (e)(1). (2) With respect to all qualified shareholders relied upon to satisfy the 50...

  14. Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number.

    PubMed

    Podhorecka, Monika; Goracy, Aneta; Szymczyk, Agnieszka; Kowal, Malgorzata; Ibanez, Blanca; Jankowska-Lecka, Olga; Macheta, Arkadiusz; Nowaczynska, Aleksandra; Drab-Urbanek, Elzbieta; Chocholska, Sylwia; Jawniak, Dariusz; Hus, Marek

    2017-05-23

    B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

  15. The Need for Nuance in the Null Hypothesis Significance Testing Debate

    ERIC Educational Resources Information Center

    Häggström, Olle

    2017-01-01

    Null hypothesis significance testing (NHST) provides an important statistical toolbox, but there are a number of ways in which it is often abused and misinterpreted, with bad consequences for the reliability and progress of science. Parts of contemporary NHST debate, especially in the psychological sciences, is reviewed, and a suggestion is made…

  16. [Significance of test results in drug hypersensitivity].

    PubMed

    Wozniak, K D

    1977-12-15

    For the diagnostics of allergic drug reactions in 2,246 patients tests of the skin and in vitro tests were carried out. As causes of the drug rashes analgetics/antipyretics, antibiotics, sulfonamides, local anaesthetics, oral anticonceptive drugs, remedies for the circulation, psychopharmaca and many others have been established. In these cases by means of skin test in 81.5%, by means of the lymphocyte transformation test in 42.9% and by means of the migration inhibition test in 35.9% of the patients a concordant result could be achieved concerning the clinical course of the disease. Relevant to practice from the results must be derived that in sensibilisation proved the avoidance of the pharmacon and of immunochemical related substances is necessary as well as principally in every anamnesis the question for drug tolerances must be asked. The possibility of the development of side effects of pharmaca when these facts are not taken into consideration is emphasized with the help of examples.

  17. When Null Hypothesis Significance Testing Is Unsuitable for Research: A Reassessment.

    PubMed

    Szucs, Denes; Ioannidis, John P A

    2017-01-01

    Null hypothesis significance testing (NHST) has several shortcomings that are likely contributing factors behind the widely debated replication crisis of (cognitive) neuroscience, psychology, and biomedical science in general. We review these shortcomings and suggest that, after sustained negative experience, NHST should no longer be the default, dominant statistical practice of all biomedical and psychological research. If theoretical predictions are weak we should not rely on all or nothing hypothesis tests. Different inferential methods may be most suitable for different types of research questions. Whenever researchers use NHST they should justify its use, and publish pre-study power calculations and effect sizes, including negative findings. Hypothesis-testing studies should be pre-registered and optimally raw data published. The current statistics lite educational approach for students that has sustained the widespread, spurious use of NHST should be phased out.

  18. When Null Hypothesis Significance Testing Is Unsuitable for Research: A Reassessment

    PubMed Central

    Szucs, Denes; Ioannidis, John P. A.

    2017-01-01

    Null hypothesis significance testing (NHST) has several shortcomings that are likely contributing factors behind the widely debated replication crisis of (cognitive) neuroscience, psychology, and biomedical science in general. We review these shortcomings and suggest that, after sustained negative experience, NHST should no longer be the default, dominant statistical practice of all biomedical and psychological research. If theoretical predictions are weak we should not rely on all or nothing hypothesis tests. Different inferential methods may be most suitable for different types of research questions. Whenever researchers use NHST they should justify its use, and publish pre-study power calculations and effect sizes, including negative findings. Hypothesis-testing studies should be pre-registered and optimally raw data published. The current statistics lite educational approach for students that has sustained the widespread, spurious use of NHST should be phased out. PMID:28824397

  19. To t-Test or Not to t-Test? A p-Values-Based Point of View in the Receiver Operating Characteristic Curve Framework.

    PubMed

    Vexler, Albert; Yu, Jihnhee

    2018-04-13

    A common statistical doctrine supported by many introductory courses and textbooks is that t-test type procedures based on normally distributed data points are anticipated to provide a standard in decision-making. In order to motivate scholars to examine this convention, we introduce a simple approach based on graphical tools of receiver operating characteristic (ROC) curve analysis, a well-established biostatistical methodology. In this context, we propose employing a p-values-based method, taking into account the stochastic nature of p-values. We focus on the modern statistical literature to address the expected p-value (EPV) as a measure of the performance of decision-making rules. During the course of our study, we extend the EPV concept to be considered in terms of the ROC curve technique. This provides expressive evaluations and visualizations of a wide spectrum of testing mechanisms' properties. We show that the conventional power characterization of tests is a partial aspect of the presented EPV/ROC technique. We desire that this explanation of the EPV/ROC approach convinces researchers of the usefulness of the EPV/ROC approach for depicting different characteristics of decision-making procedures, in light of the growing interest regarding correct p-values-based applications.

  20. Sole Dependence on Urine Testing Strips and the Ability to Identify Clinically Significant Disease: Challenging the Current Paradigm for Heme Detection in General Clinical Situations.

    PubMed

    Rothschild, Bruce

    2016-05-01

    The ability of health care professionals to provide patient care is potentially compromised when predicated on untested, although longstanding, perspectives. One such example is urinalysis testing, which has been currently simplified to use only urine testing strips for detection of microscopic hematuria. To determine whether urine testing strips are sufficient for identification of clinically significant findings in urinalysis. To determine the presence of microscopic hematuria, I examined a collection of urine specimens that had tested heme negative during the 3-month study period. Of the 342 patients from whom urine specimens were examined during this interval, 50 had microscopic hematuria, despite having tested negative for heme via urine testing strip. Also, 30% were not receiving any medication known to produce microscopic hematuria, and 18% had clinically significant pathology. Diagnosis of significant clinical pathologic manifestations would have been compromised had microscopic examination not been performed on the urine specimens from the cohort individuals. Examination of the novel approach of including microscopic examination of specimens in a specific clinical situation challenges the dominant paradigm of reliance on assaying using urine testing strips only, revealing that the current method is not only unreliable for determining microscopic hematuria but also is less than optimal in general clinical practice. The findings of this study provide evidence of the importance of microscopic evaluation as a routine component of urinalysis. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

    PubMed

    Comino, Isabel; Fernández-Bañares, Fernando; Esteve, María; Ortigosa, Luís; Castillejo, Gemma; Fambuena, Blanca; Ribes-Koninckx, Carmen; Sierra, Carlos; Rodríguez-Herrera, Alfonso; Salazar, José Carlos; Caunedo, Ángel; Marugán-Miguelsanz, J M; Garrote, José Antonio; Vivas, Santiago; Lo Iacono, Oreste; Nuñez, Alejandro; Vaquero, Luis; Vegas, Ana María; Crespo, Laura; Fernández-Salazar, Luis; Arranz, Eduardo; Jiménez-García, Victoria Alejandra; Antonio Montes-Cano, Marco; Espín, Beatriz; Galera, Ana; Valverde, Justo; Girón, Francisco José; Bolonio, Miguel; Millán, Antonio; Cerezo, Francesc Martínez; Guajardo, César; Alberto, José Ramón; Rosinach, Mercé; Segura, Verónica; León, Francisco; Marinich, Jorge; Muñoz-Suano, Alba; Romero-Gómez, Manuel; Cebolla, Ángel; Sousa, Carolina

    2016-10-01

    Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

  2. CD8+ memory T-cell inflation renders compromised CD4+ T-cell-dependent CD8+ T-cell immunity via naïve T-cell anergy.

    PubMed

    Xu, Aizhang; Freywald, Andrew; Xie, Yufeng; Li, Zejun; Xiang, Jim

    2017-01-01

    Whether inflation of CD8 + memory T (mT) cells, which is often derived from repeated prime-boost vaccinations or chronic viral infections in the elderly, would affect late CD8 + T-cell immunity is a long-standing paradox. We have previously established an animal model with mT-cell inflation by transferring ConA-stimulated monoclonal CD8 + T cells derived from Ova-specific T-cell-receptor transgenic OTI mice into irradiation-induced lymphopenic B6 mice. In this study, we also established another two animal models with mT-cell inflation by transferring, 1) ConA-stimulated monoclonal CD8 + T cells derived from lymphocytic choriomeningitis virus glycoprotein-specific T-cell-receptor transgenic P14 mice, and 2) ConA-stimulated polyclonal CD8 + T cells derived from B6.1 mice into B6 mice with irradiation-induced lymphopenia. We vaccinated these mice with recombinant Ova-expressing Listeria monocytogenes and Ova-pulsed dendritic cells, which stimulated CD4 + T cell-independent and CD4 + T-cell-dependent CD8 + T-cell responses, respectively, and assessed Ova-specific CD8 + T-cell responses by flow cytometry. We found that Ova-specific CD8 + T-cell responses derived from the latter but not the former vaccination were significantly reduced in mice with CD8 + mT-cell inflation compared to wild-type B6 mice. We determined that naïve CD8 + T cells purified from splenocytes of mice with mT-cell inflation had defects in cell proliferation upon stimulation in vitro and in vivo and upregulated T-cell anergy-associated Itch and GRAIL molecules. Taken together, our data reveal that CD8 + mT-cell inflation renders compromised CD4 + T-cell-dependent CD8 + T-cell immunity via naïve T-cell anergy, and thus show promise for the design of efficient vaccines for elderly patients with CD8 + mT-cell inflation.

  3. A generalised significance test for individual communities in networks.

    PubMed

    Kojaku, Sadamori; Masuda, Naoki

    2018-05-09

    Many empirical networks have community structure, in which nodes are densely interconnected within each community (i.e., a group of nodes) and sparsely across different communities. Like other local and meso-scale structure of networks, communities are generally heterogeneous in various aspects such as the size, density of edges, connectivity to other communities and significance. In the present study, we propose a method to statistically test the significance of individual communities in a given network. Compared to the previous methods, the present algorithm is unique in that it accepts different community-detection algorithms and the corresponding quality function for single communities. The present method requires that a quality of each community can be quantified and that community detection is performed as optimisation of such a quality function summed over the communities. Various community detection algorithms including modularity maximisation and graph partitioning meet this criterion. Our method estimates a distribution of the quality function for randomised networks to calculate a likelihood of each community in the given network. We illustrate our algorithm by synthetic and empirical networks.

  4. MASH TL-3 testing and evaluation of the TXDOT T131RC bridge rail transition.

    DOT National Transportation Integrated Search

    2013-03-01

    This project designed and crash tested a transition design for the Texas Department of Transportation (TxDOT) T131RC Bridge Rail that would meet the strength and safety performance criteria for Test Level 3 of American Association of State Highway Of...

  5. Direct Spectrum of the Benchmark T Dwarf HD 19467 B

    NASA Astrophysics Data System (ADS)

    Crepp, Justin R.; Rice, Emily L.; Veicht, Aaron; Aguilar, Jonathan; Pueyo, Laurent; Giorla, Paige; Nilsson, Ricky; Luszcz-Cook, Statia H.; Oppenheimer, Rebecca; Hinkley, Sasha; Brenner, Douglas; Vasisht, Gautam; Cady, Eric; Beichman, Charles A.; Hillenbrand, Lynne A.; Lockhart, Thomas; Matthews, Christopher T.; Roberts, Lewis C., Jr.; Sivaramakrishnan, Anand; Soummer, Remi; Zhai, Chengxing

    2015-01-01

    HD 19467 B is presently the only directly imaged T dwarf companion known to induce a measurable Doppler acceleration around a solar-type star. We present spectroscopy measurements of this important benchmark object taken with the Project 1640 integral field unit at Palomar Observatory. Our high-contrast R ≈ 30 observations obtained simultaneously across the JH bands confirm the cold nature of the companion as reported from the discovery article and determine its spectral type for the first time. Fitting the measured spectral energy distribution to SpeX/IRTF T dwarf standards and synthetic spectra from BT-Settl atmospheric models, we find that HD 19467 B is a T5.5 ± 1 dwarf with effective temperature T_eff=978+20-43 K. Our observations reveal significant methane absorption affirming its substellar nature. HD 19467 B shows promise to become the first T dwarf that simultaneously reveals its mass, age, and metallicity independent from the spectrum of light that it emits.

  6. Correcting Two-Sample "z" and "t" Tests for Correlation: An Alternative to One-Sample Tests on Difference Scores

    ERIC Educational Resources Information Center

    Zimmerman, Donald W.

    2012-01-01

    In order to circumvent the influence of correlation in paired-samples and repeated measures experimental designs, researchers typically perform a one-sample Student "t" test on difference scores. That procedure entails some loss of power, because it employs N - 1 degrees of freedom instead of the 2N - 2 degrees of freedom of the…

  7. Significant issues in proof testing: A critical appraisal

    NASA Technical Reports Server (NTRS)

    Chell, G. G.; Mcclung, R. C.; Russell, D. A.; Chang, K. J.; Donnelly, B.

    1994-01-01

    Issues which impact on the interpretation and quantification of proof test benefits are reviewed. The importance of each issue in contributing to the extra quality assurance conferred by proof testing components is discussed, particularly with respect to the application of advanced fracture mechanics concepts to enhance the flaw screening capability of a proof test analysis. Items covered include the role in proof testing of elastic-plastic fracture mechanics, ductile instability analysis, deterministic versus probabilistic analysis, single versus multiple cycle proof testing, and non-destructive examination (NDE). The effects of proof testing on subsequent service life are reviewed, particularly with regard to stress redistribution and changes in fracture behavior resulting from the overload. The importance of proof test conditions are also addressed, covering aspects related to test temperature, simulation of service environments, test media and the application of real-time NDE. The role of each issue in a proof test methodology is assessed with respect to its ability to: promote proof test practice to a state-of-the-art; aid optimization of proof test design; and increase awareness and understanding of outstanding issues.

  8. Distribution of the two-sample t-test statistic following blinded sample size re-estimation.

    PubMed

    Lu, Kaifeng

    2016-05-01

    We consider the blinded sample size re-estimation based on the simple one-sample variance estimator at an interim analysis. We characterize the exact distribution of the standard two-sample t-test statistic at the final analysis. We describe a simulation algorithm for the evaluation of the probability of rejecting the null hypothesis at given treatment effect. We compare the blinded sample size re-estimation method with two unblinded methods with respect to the empirical type I error, the empirical power, and the empirical distribution of the standard deviation estimator and final sample size. We characterize the type I error inflation across the range of standardized non-inferiority margin for non-inferiority trials, and derive the adjusted significance level to ensure type I error control for given sample size of the internal pilot study. We show that the adjusted significance level increases as the sample size of the internal pilot study increases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. NT-proBNP: Is It a More Significant Risk Factor for Mortality Than Troponin T in Incident Hemodialysis Patients?

    PubMed Central

    Oh, Hyung Jung; Lee, Mi Jung; Lee, Hye Sun; Park, Jung Tak; Han, Seung Hyeok; Yoo, Tae-Hyun; Kim, Yong-Lim; Kim, Yon Su; Yang, Chul Woo; Kim, Nam-Ho; Kang, Shin-Wook

    2014-01-01

    Abstract Numerous studies have demonstrated that cardiac biomarkers are significant predictors of cardiovascular (CV) and all-cause mortality in ESRD patients, but most of the studies were retrospective or included small numbers of patients, only prevalent dialysis patients, or measured 1 or 2 biomarkers. This study was to analyze the association between 3 cardiac biomarkers and mortality in incident HD patients. A prospective cohort of 864 incident HD patients was followed for 30 months. Based on the median values of baseline NT-proBNP, cTnT, and hsCRP, the patients were divided into “high” and “low” groups, and CV and all-cause mortality were compared between each group. Additionally, time-dependent ROC curves were constructed, and the NRI and IDI of the models with various biomarkers were calculated. The CV survival rates were significantly lower in the “high” NT-proBNP and cTnT groups compared to the corresponding “low” groups, while there was no significant difference in CV survival rate between the 2 hsCRP groups. However, all-cause mortality rates were significantly higher in all 3 “high” groups compared to each lower group. In multivariate analyses, only Ln NT-proBNP was found to be an independent predictor of mortality. Moreover, NT-proBNP was a more prognostic marker for mortality compared to cTnT. In conclusion, NT-proBNP is the biomarker that results in the most added prognostic value on top of traditional risk factors for CV and all-cause mortality in incident HD patients. PMID:25501091

  10. Significance of hydrogen breath tests in children with suspected carbohydrate malabsorption

    PubMed Central

    2014-01-01

    Background Hydrogen breath tests are noninvasive procedures frequently applied in the diagnostic workup of functional gastrointestinal disorders. Here, we review hydrogen breath test results and the occurrence of lactose, fructose and sorbitol malabsorption in pediatric patients; and determine the significance of the findings and the outcome of patients with carbohydrate malabsorption. Methods We included 206 children (88 male, 118 female, median age 10.7 years, range 3–18 years) with a total of 449 hydrogen breath tests (lactose, n = 161; fructose, n = 142; sorbitol, n = 146) into a retrospective analysis. Apart from test results, we documented symptoms, the therapeutic consequences of the test, the outcome and the overall satisfaction of the patients and families. Results In total, 204 (46%) of all breath tests were positive. Long-term follow-up data could be collected from 118 patients. Of 79 patients (67%) who were put on a diet reduced in lactose, fructose and/or sorbitol, the majority (92%, n = 73) reported the diet to be strict and only 13% (n = 10) had no response to diet. Most families (96%, n = 113) were satisfied by the test and the therapy. There were only 21 tests (5%) with a borderline result because the criteria for a positive result were only partially met. Conclusions Hydrogen breath tests can be helpful in the evaluation of children with gastrointestinal symptoms including functional intestinal disorders. If applied for a variety of carbohydrates but only where indicated, around two-third of all children have positive results. The therapeutic consequences are successfully relieving symptoms in the vast majority of patients. PMID:24575947

  11. Design and experimental results of the 1-T Bitter Electromagnet Testing Apparatus (BETA)

    NASA Astrophysics Data System (ADS)

    Bates, E. M.; Birmingham, W. J.; Romero-Talamás, C. A.

    2018-05-01

    The Bitter Electromagnet Testing Apparatus (BETA) is a 1-Tesla (T) technical prototype of the 10 T Adjustable Long Pulsed High-Field Apparatus. BETA's final design specifications are highlighted in this paper which include electromagnetic, thermal, and stress analyses. We discuss here the design and fabrication of BETA's core, vessel, cooling, and electrical subsystems. The electrical system of BETA is composed of a scalable solid-state DC breaker circuit. Experimental results display the stable operation of BETA at 1 T. These results are compared to both analytical design and finite element calculations. Experimental results validate analytical magnet designing methods developed at the Dusty Plasma Laboratory. The theoretical steady state maxima and the limits of BETA's design are explored in this paper.

  12. Design and experimental results of the 1-T Bitter Electromagnet Testing Apparatus (BETA).

    PubMed

    Bates, E M; Birmingham, W J; Romero-Talamás, C A

    2018-05-01

    The Bitter Electromagnet Testing Apparatus (BETA) is a 1-Tesla (T) technical prototype of the 10 T Adjustable Long Pulsed High-Field Apparatus. BETA's final design specifications are highlighted in this paper which include electromagnetic, thermal, and stress analyses. We discuss here the design and fabrication of BETA's core, vessel, cooling, and electrical subsystems. The electrical system of BETA is composed of a scalable solid-state DC breaker circuit. Experimental results display the stable operation of BETA at 1 T. These results are compared to both analytical design and finite element calculations. Experimental results validate analytical magnet designing methods developed at the Dusty Plasma Laboratory. The theoretical steady state maxima and the limits of BETA's design are explored in this paper.

  13. Targeted Sos1 deletion reveals its critical role in early T-cell development

    PubMed Central

    Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Li, Wenmei; Grinberg, Alex; Lee, Jan; Love, Paul E.; Samelson, Lawrence E.

    2011-01-01

    Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development. PMID:21746917

  14. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

    PubMed Central

    Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

    2014-01-01

    A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

  15. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.

    PubMed

    Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

    2014-08-01

    A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis.

  16. Effect of education and language on baseline concussion screening tests in professional baseball players.

    PubMed

    Jones, Nathaniel S; Walter, Kevin D; Caplinger, Roger; Wright, Daniel; Raasch, William G; Young, Craig

    2014-07-01

    The purpose of the present study was to investigate the possible effects of sociocultural influences, specifically pertaining to language and education, on baseline neuropsychological concussion testing as obtained via immediate postconcussion assessment and cognitive testing (ImPACT) of players from a professional baseball team. A retrospective chart review. Baseline testing of a professional baseball organization. Four hundred five professional baseball players. Age, languages spoken, hometown country location (United States/Canada vs overseas), and years of education. The 5 ImPACT composite scores (verbal memory, visual memory, visual motor speed, reaction time, impulse control) and ImPACT total symptom score from the initial baseline testing. The result of t tests revealed significant differences (P < 0.05) when comparing native English to native Spanish speakers in many scores. Even when corrected for education, the significant differences (P < 0.05) remained in some scores. Sociocultural differences may result in differences in computer-based neuropsychological testing scores.

  17. Tn-seq of Caulobacter crescentus under uranium stress reveals genes essential for detoxification and stress tolerance

    DOE PAGES

    Yung, Mimi C.; Park, Dan M.; Overton, K. Wesley; ...

    2015-07-20

    Ubiquitous aquatic bacterium Caulobacter crescentus is highly resistant to uranium (U) and facilitates U biomineralization and thus holds promise as an agent of U bioremediation. In order to gain an understanding of how C. crescentus tolerates U, we employed transposon (Tn) mutagenesis paired with deep sequencing (Tn-seq) in a global screen for genomic elements required for U resistance. Of the 3,879 annotated genes in the C. crescentus genome, 37 were found to be specifically associated with fitness under U stress, 15 of which were subsequently tested through mutational analysis. Systematic deletion analysis revealed that mutants lacking outer membrane transporters (rsaFamore » and rsaFb), a stress-responsive transcription factor (cztR), or a ppGpp synthetase/hydrolase (spoT) exhibited a significantly lower survival rate under U stress. RsaFa and RsaFb, which are homologues of TolC in Escherichia coli, have previously been shown to mediate S-layer export. Transcriptional analysis revealed upregulation of rsaF a and rsaF b by 4- and 10-fold, respectively, in the presence of U. We additionally show that rsaFa mutants accumulated higher levels of U than the wild type, with no significant increase in oxidative stress levels. These results suggest a function for RsaF a and RsaF b in U efflux and/or maintenance of membrane integrity during U stress. In addition, we present data implicating CztR and SpoT in resistance to U stress. Together, our findings reveal novel gene targets that are key to understanding the molecular mechanisms of U resistance in C. crescentus.« less

  18. 77 FR 19861 - Certain Polybrominated Diphenylethers; Significant New Use Rule and Test Rule

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-02

    ...The Agency is proposing to amend the Toxic Substances Control Act (TSCA) section 5(a) Significant New Use Rule (SNUR), for certain polybrominated diphenylethers (PBDEs) by: Designating processing of six PBDEs, or any combination of these chemical substances resulting from a chemical reaction, as a significant new use; designating manufacturing, importing, and processing of a seventh PBDE, decabromodiphenyl ether (decaBDE) for any use which is not ongoing after December 31, 2013, as a significant new use; and making inapplicable the article exemption for SNURs for this action. A person who intends to import or process any of the seven PBDEs included in the proposed SNUR, as part of an article for a significant new use would be required to notify EPA at least 90 days in advance to ensure that the Agency has an opportunity to review and, if necessary, restrict or prohibit a new use before it begins. EPA is also proposing a test rule under TSCA that would require any person who manufactures or processes commercial pentabromodiphenyl ether (c-pentaBDE), commercial octabromodiphenyl ether (c-octaBDE), or commercial decaBDE (c-decaBDE), including in articles, for any use after December 31, 2013, to conduct testing on their effects on health and the environment. EPA is proposing to designate all discontinued uses of PBDEs as significant new uses. The test rule would be promulgated if EPA determines that there are persons who intend to manufacture, import, or process c-pentaBDE, c-octaBDE, or c-decaBDE, for any use, including in articles, after December 31, 2013.

  19. Curcumin up regulates T helper 1 cells in patients with colon cancer.

    PubMed

    Xu, Bin; Yu, Lin; Zhao, Li-Zhong

    2017-01-01

    The therapy for the advanced colon cancer (Cca) is unsatisfactory currently. To regulate the immune effector cell function has shown a positive effect on the treatment of advanced cancers. This study tests a hypothesis that administration with curcumin converts the Cca patient-derived regulatory T cells (Treg) to T helper (Th) 1 cells. In this study, a group of patients with advanced Cca was recruited into this study. The patients were treated with curcumin. The peripheral Tregs and Th1 cells were assessed by flow cytometry. The results showed that, after the curcumin therapy, the forkhead box protein (Foxp) 3 positive Treg frequency was markedly reduced, the frequency of Th1 cells was significantly increased in Cca patients. Treating with curcumin repressed the Foxp3 gene transcription in Tregs; the Tregs were then converted into Th1 cells. The results also revealed that Foxp3 bound T-bet to prevent IFN-γ expression in CD4 + T cells, which was abolished by treating with curcumin. In conclusion, the administration of curcumin can convert Tregs to Th1 cells via repressing Foxp3 expression and enhancing IFN-γ production.

  20. Whole transcriptome analysis reveals dysregulated oncogenic lncRNAs in natural killer/T-cell lymphoma and establishes MIR155HG as a target of PRDM1.

    PubMed

    Baytak, Esra; Gong, Qiang; Akman, Burcu; Yuan, Hongling; Chan, Wing C; Küçük, Can

    2017-05-01

    Natural killer/T-cell lymphoma is a rare but aggressive neoplasm with poor prognosis. Despite previous reports that showed potential tumor suppressors, such as PRDM1 or oncogenes associated with the etiology of this malignancy, the role of long non-coding RNAs in natural killer/T-cell lymphoma pathobiology has not been addressed to date. Here, we aim to identify cancer-associated dysregulated long non-coding RNAs and signaling pathways or biological processes associated with these long non-coding RNAs in natural killer/T-cell lymphoma cases and to identify the long non-coding RNAs transcriptionally regulated by PRDM1. RNA-Seq analysis revealed 166 and 66 long non-coding RNAs to be significantly overexpressed or underexpressed, respectively, in natural killer/T-cell lymphoma cases compared with resting or activated normal natural killer cells. Novel long non-coding RNAs as well as the cancer-associated ones such as SNHG5, ZFAS1, or MIR155HG were dysregulated. Interestingly, antisense transcripts of many growth-regulating genes appeared to be transcriptionally deregulated. Expression of ZFAS1, which is upregulated in natural killer/T-cell lymphoma cases, showed association with growth-regulating pathways such as stabilization of P53, regulation of apoptosis, cell cycle, or nuclear factor-kappa B signaling in normal and neoplastic natural killer cell samples. Consistent with the tumor suppressive role of PRDM1, we identified MIR155HG and TERC to be transcriptionally downregulated by PRDM1 in two PRDM1-null NK-cell lines when it is ectopically expressed. In conclusion, this is the first study that identified long non-coding RNAs whose expression is dysregulated in natural killer/T-cell lymphoma cases. These findings suggest that ZFAS1 and other dysregulated long non-coding RNAs may be involved in natural killer/T-cell lymphoma pathobiology through regulation of cancer-related genes, and loss-of-PRDM1 expression in natural killer/T-cell lymphomas may contribute to

  1. 10 CFR Appendix T to Subpart B of... - Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals T Appendix T to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Test Procedures Pt. 430, Subpt. B, App. T Appendix T to Subpart B of Part 430—Uniform...

  2. 10 CFR Appendix T to Subpart B of... - Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals T Appendix T to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Test Procedures Pt. 430, Subpt. B, App. T Appendix T to Subpart B of Part 430—Uniform...

  3. 10 CFR Appendix T to Subpart B of... - Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals T Appendix T to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Test Procedures Pt. 430, Subpt. B, App. T Appendix T to Subpart B of Part 430—Uniform...

  4. 10 CFR Appendix T to Subpart B of... - Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals T Appendix T to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Test Procedures Pt. 430, Subpt. B, App. T Appendix T to Subpart B of Part 430—Uniform...

  5. 10 CFR Appendix T to Subpart B of... - Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Uniform Test Method for Measuring the Water Consumption of Water Closets and Urinals T Appendix T to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Test Procedures Pt. 430, Subpt. B, App. T Appendix T to Subpart B of Part 430—Uniform...

  6. The uriscreen test to detect significant asymptomatic bacteriuria during pregnancy.

    PubMed

    Teppa, Roberto J; Roberts, James M

    2005-01-01

    Asymptomatic bacteriuria (ASB) occurs in 2-11% of pregnancies and it is a clear predisposition to the development of acute pyelonephritis, which, in turn, poses risk to mother and fetus. Treatment of bacteriuria during pregnancy reduces the incidence of pyelonephritis. Therefore, it is recommended to screen for ASB at the first prenatal visit. The gold standard for detection of bacteriuria during pregnancy is urine culture, but this test is expensive, time-consuming, and labor-intensive. To determine the reliability of an enzymatic urine screening test (Uriscreen; Savyon Diagnostics, Ashdod, Israel) for detecting ASB in pregnancy. Catheterized urine samples were collected from 150 women who had routine prenatal screening for ASB. Patients with urinary symptoms, active vaginal bleeding, or who were previously on antibiotics therapy were excluded from the study. Sensitivity, specificity, and the positive and negative predictive values for the Uriscreen were estimated using urine culture as the criterion standard. Urine cultures were considered positive if they grew >10(5) colony-forming units of a single uropathogen. Twenty-eight women (18.7%) had urine culture results indicating significant bacteriuria, and 17 of these 28 specimens had positive enzyme activity. Of 122 samples with no growth, 109 had negative enzyme activity. Sensitivity, specificity, and positive and negative predictive values for the Uriscreen test were 60.7% (+/-18.1), 89.3% (+/-5.6), 56.6%, and 90.8%, respectively. The Uriscreen test had inadequate sensitivity for rapid screening of bacteriuria in pregnancy.

  7. Significant-Loophole-Free Test of Bell's Theorem with Entangled Photons.

    PubMed

    Giustina, Marissa; Versteegh, Marijn A M; Wengerowsky, Sören; Handsteiner, Johannes; Hochrainer, Armin; Phelan, Kevin; Steinlechner, Fabian; Kofler, Johannes; Larsson, Jan-Åke; Abellán, Carlos; Amaya, Waldimar; Pruneri, Valerio; Mitchell, Morgan W; Beyer, Jörn; Gerrits, Thomas; Lita, Adriana E; Shalm, Lynden K; Nam, Sae Woo; Scheidl, Thomas; Ursin, Rupert; Wittmann, Bernhard; Zeilinger, Anton

    2015-12-18

    Local realism is the worldview in which physical properties of objects exist independently of measurement and where physical influences cannot travel faster than the speed of light. Bell's theorem states that this worldview is incompatible with the predictions of quantum mechanics, as is expressed in Bell's inequalities. Previous experiments convincingly supported the quantum predictions. Yet, every experiment requires assumptions that provide loopholes for a local realist explanation. Here, we report a Bell test that closes the most significant of these loopholes simultaneously. Using a well-optimized source of entangled photons, rapid setting generation, and highly efficient superconducting detectors, we observe a violation of a Bell inequality with high statistical significance. The purely statistical probability of our results to occur under local realism does not exceed 3.74×10^{-31}, corresponding to an 11.5 standard deviation effect.

  8. Mitochondrial tRNALeu(UUR) C3275T, tRNAGln T4363C and tRNALys A8343G mutations may be associated with PCOS and metabolic syndrome.

    PubMed

    Ding, Yu; Xia, Bo-Hou; Zhang, Cai-Juan; Zhuo, Guang-Chao

    2018-02-05

    Polycystic ovary syndrome (PCOS) is a very prevalent endocrine disease affecting reproductive women. Clinically, patients with this disorder are more vulnerable to develop type 2 diabetes mellitus (T2DM), cardiovascular events, as well as metabolic syndrome (MetS). To date, the molecular mechanism underlying PCOS remains largely unknown. Previously, we showed that mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutation was an important cause for PCOS. In the current study, we described the clinical and biochemical features of a three-generation pedigree with maternally transmitted MetS, combined with PCOS. A total of three matrilineal relatives exhibited MetS including obesity, high triglyceride (TG) and Hemoglobin A1c (HbA1c) levels, and hypertension. Whereas one patient from the third generation manifestated PCOS. Mutational analysis of the whole mitochondrial genes from the affected individuals identified a set of genetic variations belonging to East Asia haplogroup B4b1c. Among these variants, the homoplasmic C3275T mutation disrupted a highly evolutionary conserved base-pairing (28A-46C) on the variable region of tRNA Leu(UUR) , whereas the T4363C mutation created a new base-pairing (31T-37A) in the anticodon stem of tRNA Gln , furthermore, the A8343G mutation occurred at the very conserved position of tRNA Lys and may result the failure in mitochondrial tRNAs (mt-tRNAs) metabolism. Biochemical analysis revealed the deficiency in mitochondrial functions including lower levels of mitochondrial membrane potential (MMP), ATP production and mtDNA copy number, while a significantly increased reactive oxygen species (ROS) generation was observed in polymononuclear leukocytes (PMNs) from the individuals carrying these mt-tRNA mutations, suggesting that these mutations may cause mitochondrial dysfunction that was responsible for the clinical phenotypes. Taken together, our data indicated that mt-tRNA mutations were associated with MetS and PCOS in this

  9. The benefits of the 3T3 NRU test in the safety assessment of cosmetics: long-term experience from pre-marketing testing in the Czech Republic.

    PubMed

    Jírová, D; Kejlová, K; Brabec, M; Bendová, H; Kolárová, H

    2003-01-01

    We have introduced the 3T3 NRU cytotoxicity test for methodological, economical and ethical reasons as a regular part of tier pre-marketing testing to assess local tolerance of raw materials for cosmetics, household chemicals and final cosmetic products. Using the 3T3 cell line according to the standard INVITTOX protocol No.64 (NRU Assay) the borderline concentration, relevant to the highest tolerated dose, is determined for each material. The toxic effect is reached at different concentration levels specific for individual cosmetics categories, depending on their chemical characteristics. Typical ranges of cytotoxicity for specific categories of cosmetics were established after testing of hundreds of materials. The range lies between 1 microg/ml (anti-dandruff shampoos), up to 2000 microg/ml (toothpastes and mouthwashes). The 3T3 NRU cytotoxicity test is a sensitive tool able to identify more aggressive products, that are also more likely to evoke irritation in human skin. It was even possible to detect protective effects of one natural herbal ingredient. The comparative study of cytotoxicity test results and human patch test results from a group of essential oils is presented. Cytotoxicity tests represent a highly ethical approach for estimation of irritancy. On the basis of in vitro test results suggesting low risk we can proceed to confirmatory tests in human volunteers.

  10. Further Estimates of (T-T_{90}) Close to the Triple Point of Water

    NASA Astrophysics Data System (ADS)

    Underwood, R.; de Podesta, M.; Sutton, G.; Stanger, L.; Rusby, R.; Harris, P.; Morantz, P.; Machin, G.

    2017-03-01

    Recent advances in primary acoustic gas thermometry (AGT) have revealed significant differences between temperature measurements using the International Temperature Scale of 1990, T_{90}, and thermodynamic temperature, T. In 2015, we published estimates of the differences (T-T_{90}) from 118 K to 303 K, which showed interesting behavior in the region around the triple point of water, T_TPW=273.16 K. In that work, the T_{90} measurements below T_TPW used a different ensemble of capsule standard platinum resistance thermometers (SPRTs) than the T_{90} measurements above T_TPW. In this work, we extend our earlier measurements using the same ensemble of SPRTs above and below T_TPW, enabling a deeper analysis of the slope d(T-T_{90})/dT around T_TPW. In this article, we present the results of seven AGT isotherms in the temperature range 258 K to 323 K. The derived values of (T-T_{90}) have exceptionally low uncertainties and are in good agreement with our previous data and other AGT results. We present the values (T-T_{90}) alongside our previous estimates, with the resistance ratios W( T) from two SPRTs which have been used across the full range 118 K to 323 K. Additionally, our measurements show discontinuities in d(T-T_{90})/dT at T_TPW which are consistent with the slope discontinuity in the SPRT deviation functions. Since this discontinuity is by definition non-unique, and can take a range of values including zero, we suggest that mathematical representations of (T-T_{90}), such as those in the mise en pratique for the kelvin (Fellmuth et al. in Philos Trans R Soc A 374:20150037, 2016. doi: 10.1098/rsta.2015.0037), should have continuity of d(T-T_{90})/dT at T_TPW.

  11. Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

    PubMed Central

    Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng

    2016-01-01

    Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492

  12. Disease-aging network reveals significant roles of aging genes in connecting genetic diseases.

    PubMed

    Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun

    2009-09-01

    One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.

  13. Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15.

    PubMed

    Inukai, Takeshi; Kiyokawa, Nobutaka; Campana, Dario; Coustan-Smith, Elaine; Kikuchi, Akira; Kobayashi, Miyuki; Takahashi, Hiroyuki; Koh, Katsuyoshi; Manabe, Atsushi; Kumagai, Masaaki; Ikuta, Koichiro; Hayashi, Yasuhide; Tsuchida, Masahiro; Sugita, Kanji; Ohara, Akira

    2012-02-01

    Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL. © 2011 Blackwell Publishing Ltd.

  14. Antimicrobial Activity and Chemical Composition of "Kpètè-Kpètè": A Starter of Benin Traditional Beer Tchoukoutou.

    PubMed

    N'tcha, Christine; Sina, Haziz; Kayodé, Adéchola Pierre Polycarpe; Gbenou, Joachim D; Baba-Moussa, Lamine

    2017-01-01

    The aim of this study was to investigate the antibacterial effect of the crude starter " kpètè-kpètè " and lactic acid bacteria used during the production of "tchoukoutou." To achieve this, a total of 11 lactic acid bacteria and 40 starter samples were collected from four communes. The samples were tested on 29 gram + and - strains by disk diffusion method. The minimum inhibitory and bactericidal concentrations of starter and lactic acid bacteria were determined by conventional methods. Organic acids, sugar, and volatile compounds were determined using the HPLC method. The "kpètè-kpètè" displays a high antibacterial activity against the tested strains. The most sensitive strain was S. epidermidis (12.5 mm) whereas the resistance strain was Proteus mirabilis (8 mm). All the tested ferment has not any inhibitory effect on Enterococcus faecalis . The lactic acid bacteria isolates of Parakou showed the highest (17.48 mm) antibacterial activity whereas the smallest diameter was obtained with the ferment collected from Boukoumbé (9.80 mm). The starters' chemical screening revealed the presence of tannins, anthocyanin flavonoids, triterpenes, steroids, reducing compounds, and mucilage O-glycosides. These compounds are probably the source of recorded inhibition effect. The lactic acid bacteria of the "kpètè-kpètè" could be used to develop a food ingredient with probiotic property.

  15. Start Codon Targeted (SCoT) marker reveals genetic diversity of Dendrobium nobile Lindl., an endangered medicinal orchid species.

    PubMed

    Bhattacharyya, Paromik; Kumaria, Suman; Kumar, Shrawan; Tandon, Pramod

    2013-10-15

    Genetic variability in the wild genotypes of Dendrobium nobile Lindl. collected from different parts of Northeast India, was analyzed using a Start Codon Targeted (SCoT) marker system. A total of sixty individuals comprising of six natural populations were investigated for the existing natural genetic diversity. One hundred and thirty two (132) amplicons were produced by SCoT marker generating 96.21% polymorphism. The PIC value of the SCoT marker system was 0.78 and the Rp values of the primers ranged between 4.43 and 7.50. The percentage of polymorphic loci (Pp) ranging from 25% to 56.82%, Nei's gene diversity (h) from 0.08 to 0.15 with mean Nei's gene diversity of 0.28, and Shannon's information index (I) values ranging from 0.13 to 0.24 with an average value of 0.43 were recorded. The gene flow value (0.37) and the diversity among populations (0.57) demonstrated higher genetic variation among the populations. Analysis of molecular variance (AMOVA) showed 43.37% of variation within the populations, whereas 56.63% variation was recorded among the populations. Cluster analysis also reveals high genetic variation among the genotypes. Present investigation suggests the effectiveness of SCoT marker system to estimate the genetic diversity of D. nobile and that it can be seen as a preliminary point for future research on the population and evolutionary genetics of this endangered orchid species of medicinal importance. © 2013.

  16. Fast and Accurate Approximation to Significance Tests in Genome-Wide Association Studies

    PubMed Central

    Zhang, Yu; Liu, Jun S.

    2011-01-01

    Genome-wide association studies commonly involve simultaneous tests of millions of single nucleotide polymorphisms (SNP) for disease association. The SNPs in nearby genomic regions, however, are often highly correlated due to linkage disequilibrium (LD, a genetic term for correlation). Simple Bonferonni correction for multiple comparisons is therefore too conservative. Permutation tests, which are often employed in practice, are both computationally expensive for genome-wide studies and limited in their scopes. We present an accurate and computationally efficient method, based on Poisson de-clumping heuristics, for approximating genome-wide significance of SNP associations. Compared with permutation tests and other multiple comparison adjustment approaches, our method computes the most accurate and robust p-value adjustments for millions of correlated comparisons within seconds. We demonstrate analytically that the accuracy and the efficiency of our method are nearly independent of the sample size, the number of SNPs, and the scale of p-values to be adjusted. In addition, our method can be easily adopted to estimate false discovery rate. When applied to genome-wide SNP datasets, we observed highly variable p-value adjustment results evaluated from different genomic regions. The variation in adjustments along the genome, however, are well conserved between the European and the African populations. The p-value adjustments are significantly correlated with LD among SNPs, recombination rates, and SNP densities. Given the large variability of sequence features in the genome, we further discuss a novel approach of using SNP-specific (local) thresholds to detect genome-wide significant associations. This article has supplementary material online. PMID:22140288

  17. A procedure for the significance testing of unmodeled errors in GNSS observations

    NASA Astrophysics Data System (ADS)

    Li, Bofeng; Zhang, Zhetao; Shen, Yunzhong; Yang, Ling

    2018-01-01

    It is a crucial task to establish a precise mathematical model for global navigation satellite system (GNSS) observations in precise positioning. Due to the spatiotemporal complexity of, and limited knowledge on, systematic errors in GNSS observations, some residual systematic errors would inevitably remain even after corrected with empirical model and parameterization. These residual systematic errors are referred to as unmodeled errors. However, most of the existing studies mainly focus on handling the systematic errors that can be properly modeled and then simply ignore the unmodeled errors that may actually exist. To further improve the accuracy and reliability of GNSS applications, such unmodeled errors must be handled especially when they are significant. Therefore, a very first question is how to statistically validate the significance of unmodeled errors. In this research, we will propose a procedure to examine the significance of these unmodeled errors by the combined use of the hypothesis tests. With this testing procedure, three components of unmodeled errors, i.e., the nonstationary signal, stationary signal and white noise, are identified. The procedure is tested by using simulated data and real BeiDou datasets with varying error sources. The results show that the unmodeled errors can be discriminated by our procedure with approximately 90% confidence. The efficiency of the proposed procedure is further reassured by applying the time-domain Allan variance analysis and frequency-domain fast Fourier transform. In summary, the spatiotemporally correlated unmodeled errors are commonly existent in GNSS observations and mainly governed by the residual atmospheric biases and multipath. Their patterns may also be impacted by the receiver.

  18. Breast MRI at 3.0 T in a high-risk familial breast cancer screening cohort: comparison with 1.5 T screening studies.

    PubMed

    Pickles, M D; Turnbull, L W

    2012-07-01

    The sensitivity of X-ray mammography for the detection of breast malignancy in younger females is lower than that of breast MRI; consequently, guidelines recommend annual MRI for patients with a significantly elevated lifetime risk. The improved signal-to-noise ratio obtainable at 3.0 T should result in data superior to those obtainable at 1.5 T. However, breast imaging on higher field strength systems poses specific problems. As a result, caution has been urged in the implementation of breast MRI at 3.0 T. The aim of this study was to determine if it is appropriate to use 3.0 T MRI in the screening of patients by comparing the summary statistics achieved by this 3.0 T MRI programme against the published results of 1.5 T screening studies. Over a 20-month period, 291 patients referred with an elevated familial risk of breast cancer were examined at 3.0 T. Resulting images were scored based on the Royal College of Radiologists Breast Group imaging classification. The reference standard was a combination of histology and follow-up imaging. Follow-up data were available in 267 patients. Analysis revealed positive and negative post-test probabilities of 28% [95% confidence intervals (CI); range, 10-60%] and 1% (95% CI; range, 0-2%), respectively. These results compared favourably against those of a recent meta-analysis [25.3% (95% CI; range, 18.4-33.8%) and 0.4% (95% CI; range, 0.2-0.9%), respectively]. Given the similar summary statistics between this work and the 1.5 T results, it would appear that screening of high-risk patients at 3.0 T has potential. Further studies should be undertaken to verify this result.

  19. EEG Driven tDCS Versus Bifrontal tDCS for Tinnitus

    PubMed Central

    De Ridder, Dirk; Vanneste, Sven

    2012-01-01

    Tinnitus is the perception of a sound in the absence of any objective physical sound source. Transcranial Direct Current Stimulation (tDCS) induces shifts in membrane resting potentials depending on the polarity of the stimulation: under the anode gamma band activity increases, whereas under the cathode the opposite occurs. Both single and multiple sessions of tDCS over the dorsolateral prefrontal cortex (DLPFC; anode over right DLPFC) yield a transient improvement in tinnitus intensity and tinnitus distress. The question arises whether optimization of the tDCS protocol can be obtained by using EEG driven decisions on where to place anode and cathode. Using gamma band functional connectivity could be superior to gamma band activity as functional connectivity determines the tinnitus network in many aspects of chronic tinnitus. Six-hundred-seventy-five patients were included in the study: 265 patients received tDCS with cathodal electrode placed over the left DLPFC and the anode placed overlying the right DLPFC, 380 patients received tDCS based on EEG connectivity, and 65 received no tDCS (i.e., waiting list control group). Repeated measures ANOVA revealed a significant main effect for pre versus post measurement. Bifrontal tDCS in comparison to EEG driven tDCS had a larger reduction for both tinnitus distress and tinnitus intensity. Whereas the results of the bifrontal tDCS seem to confirm previous studies, the use of gamma band functional connectivity seems not to bring any advantage to tDCS for tinnitus suppression. Using other potential biomarkers, such as gamma band activity, or theta functional connectivity could theoretically be of use. Further studies will have to elucidate whether brain state based tDCS has any advantages over “blind” bifrontal stimulation. PMID:23055986

  20. Mechanistic insights into the link between visfatin gene C-1535T polymorphism and coronary artery disease: an in vitro study.

    PubMed

    Wang, Yong-Sheng; Gao, Wei; Li, Hong-Fen; Wang, Ze-Mu; Zhu, Jun; Zhao, Huan; Yan, Jian-Jun; Jia, En-Zhi; Yang, Zhi-Jian; Wang, Lian-Sheng

    2012-04-01

    Visfatin, a pro-inflammatory cytokine predominantly released from leucocytes, is correlated with coronary artery disease (CAD). We have previously reported that the -1535C>T polymorphism (rs1330082), which located on the promoter region of visfatin, was associated with decreased risk of CAD. Here, we investigated the underlying mechanism by which this polymorphism affects the genetic susceptibility to CAD. The difference of the promoter activities between -1535T variant and -1535C allele was tested by luciferase reporter gene assay. The difference of transcription factor binding activities between T and C allele was evaluated by electrophoretic mobility shift assay. In reporter gene assay, we showed that the T variant had a significantly reduced transcriptional activity compared with the C allele. The T-variant significantly attenuated the promoter binding affinity to nuclear transcription factors and this effect became much obvious after treatment with TNF-α. Moreover, competition experiment revealed that the retarded complex formed by T-1535- or C-1535-probe binding to nuclear extracts was nearly completely inhibited by unlabeled activator protein-1 (AP-1) specific probe, indicating that AP-1 might be the target nuclear effector. Taken together, our data provided potential mechanistic link between the visfatin -1535C>T polymorphism and reduced CAD risk.

  1. Analysis of CFRP Joints by Means of T-Pull Mechanical Test and Ultrasonic Defects Detection.

    PubMed

    Casavola, Caterina; Palano, Fania; De Cillis, Francesco; Tati, Angelo; Terzi, Roberto; Luprano, Vincenza

    2018-04-18

    Defects detection within a composite component, with the aim of understanding and predicting its mechanical behavior, is of great importance in the aeronautical field because the irregularities of the composite material could compromise functionality. The aim of this paper is to detect defects by means of non-destructive testing (NDT) on T-pull samples made by carbon fiber reinforced polymers (CFRP) and to evaluate their effect on the mechanical response of the material. Samples, obtained from an industrial stringer having an inclined web and realized with a polymeric filler between cap and web, were subjected to ultrasonic monitoring and then to T-pull mechanical tests. All samples were tested with the same load mode and the same test configuration. An experimental set-up consisting of a semiautomatic C-scan ultrasonic mapping system with a phased array probe was designed and developed, optimizing control parameters and implementing image processing software. The present work is carried out on real composites parts that are characterized by having their intrinsic defectiveness, as opposed to the previous similar results in the literature mainly obtained on composite parts with artificially produced defects. In fact, although samples under study were realized free from defects, ultrasonic mapping found defectiveness inside the material. Moreover, the ultrasonic inspection could be useful in detecting both the location and size of defects. Experimental data were critically analyzed and qualitatively correlated with results of T-pull mechanical tests in order to better understand and explain mechanical behavior in terms of fracture mode.

  2. Analysis of CFRP Joints by Means of T-Pull Mechanical Test and Ultrasonic Defects Detection

    PubMed Central

    Casavola, Caterina; Palano, Fania; De Cillis, Francesco; Tati, Angelo; Terzi, Roberto; Luprano, Vincenza

    2018-01-01

    Defects detection within a composite component, with the aim of understanding and predicting its mechanical behavior, is of great importance in the aeronautical field because the irregularities of the composite material could compromise functionality. The aim of this paper is to detect defects by means of non-destructive testing (NDT) on T-pull samples made by carbon fiber reinforced polymers (CFRP) and to evaluate their effect on the mechanical response of the material. Samples, obtained from an industrial stringer having an inclined web and realized with a polymeric filler between cap and web, were subjected to ultrasonic monitoring and then to T-pull mechanical tests. All samples were tested with the same load mode and the same test configuration. An experimental set-up consisting of a semiautomatic C-scan ultrasonic mapping system with a phased array probe was designed and developed, optimizing control parameters and implementing image processing software. The present work is carried out on real composites parts that are characterized by having their intrinsic defectiveness, as opposed to the previous similar results in the literature mainly obtained on composite parts with artificially produced defects. In fact, although samples under study were realized free from defects, ultrasonic mapping found defectiveness inside the material. Moreover, the ultrasonic inspection could be useful in detecting both the location and size of defects. Experimental data were critically analyzed and qualitatively correlated with results of T-pull mechanical tests in order to better understand and explain mechanical behavior in terms of fracture mode. PMID:29669992

  3. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids.

    PubMed

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M; Söll, Dieter

    2015-12-15

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNA(Pyl) to create tRNA(Pyl-opt) with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (N(ϵ)-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNA(Pyl-opt) facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNA(Pyl-opt) with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNA(Pyl-opt) had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNA(Pyl-opt) should be an excellent replacement of wild-type tRNA(Pyl) for future ncAA incorporation by PylRS enzymes. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Significant decreases in blood propofol concentrations during adrenalectomy for phaeochromocytoma.

    PubMed

    Watanabe, Tatsunori; Hiraoka, Haruhiko; Araki, Takuya; Nagano, Daisuke; Aomori, Tohru; Nakamura, Tomonori; Yamamoto, Koujirou; Baba, Hiroshi

    2017-10-01

    The kinetics of propofol are influenced by cardiac output. The aim of this study was to examine changes in blood propofol concentrations during phaeochromocytoma surgery using target-controlled infusion (TCI) anaesthesia with propofol. This is a prospective observational study. Ten patients with phaeochromocytoma who underwent unilateral adrenalectomy were included. Cardiac output was measured using an arterial pressure-based cardiac output analysis method. The target blood propofol concentrations were adjusted to maintain an approximate bispectral index (BIS) value of 40 before initiating surgery. The settings remained constant during surgery. Blood samples for propofol concentrations were collected from the radial artery at seven time points: two before tumour manipulation (T1, 2), two during tumour manipulation (T3, 4), and three after tumour vein ligation (T4-7). BIS values, the arterial pressure cardiac index (APCI) and haemodynamic parameters were measured at the same time points as the blood samples. The prop-ratio was calculated by dividing blood propofol concentrations by target concentrations of TCI. APCI increased during tumour manipulation and after tumour vein ligation. The prop-ratio was reduced significantly by approximately 40% and showed a significant negative correlation with APCI. BIS values increased significantly and showed a significant negative correlation with the prop-ratio. The increased APCI during tumour manipulation and after tumour vein ligation was associated with markedly reduced blood propofol concentrations. These results reveal that significant decreases in the anaesthetic effect may be observed in patients undergoing phaeochromocytoma surgery even if TCI anaesthesia is used with propofol. © 2017 The British Pharmacological Society.

  5. Yawed-Rolling Tire Mechanical Properties Testing of the Navy T-45 Aircraft Tires

    NASA Technical Reports Server (NTRS)

    Daugherty, Robert H.

    2000-01-01

    The T-45 Goshawk is a United States Navy Jet aircraft used primarily as a trainer. The aircraft design makes use of "off the shelf" hardware as much as possible and was found to have unusual directional control issues during around operations. The aircraft was involved in numerous pilot-induced-oscillation incidents as well as observed to have unusual directional control reactions to failed main gear tires, a condition that is normally handled relatively easily by conventional aircraft steering control techniques. The behavior of the aircraft's tires had previously been modeled in simulators as a result of approximations provided in 40-year-old reference publications. Since knowledge of the true tire cornering and braking behavior is essential to modeling, understanding, and fixing directional control problems, the United States Navy requested assistance from the NASA Langley Research Center's (LARC) Aircraft Landing Dynamics Facility (ALDF) to define the yawed-rolling mechanical properties of the T-45 aircraft tires. The purpose of this report is to document the results of testing the subject tires at the NASA LaRC ALDF in September 1998. Brief descriptions of the Instrumented Tire Test Vehicle (ITTV) are included to familiarize the reader with the ITTV capabilities, data acquisition system, test and measurement techniques, data accuracy, and analysis and presentation of the testing results.

  6. Significance Testing in Confirmatory Factor Analytic Models.

    ERIC Educational Resources Information Center

    Khattab, Ali-Maher; Hocevar, Dennis

    Traditionally, confirmatory factor analytic models are tested against a null model of total independence. Using randomly generated factors in a matrix of 46 aptitude tests, this approach is shown to be unlikely to reject even random factors. An alternative null model, based on a single general factor, is suggested. In addition, an index of model…

  7. Periorbital edema as the initial presentation of T-cell prolymphocytic leukemia.

    PubMed

    Nusz, Kevin J; Pang, Noelene K; Woog, John J

    2006-01-01

    A 57-year-old woman presented with a history of progressive bilateral upper and lower eyelid edema. Laboratory tests revealed T-cell prolymphocytic leukemia. Despite systemic treatment, she died 2 weeks after presentation. This life-threatening disorder should be added to the differential diagnosis of eyelid edema.

  8. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients

    PubMed Central

    Comino, Isabel; Fernández-Bañares, Fernando; Esteve, María; Ortigosa, Luís; Castillejo, Gemma; Fambuena, Blanca; Ribes-Koninckx, Carmen; Sierra, Carlos; Rodríguez-Herrera, Alfonso; Salazar, José Carlos; Caunedo, Ángel; Marugán-Miguelsanz, J M; Garrote, José Antonio; Vivas, Santiago; lo Iacono, Oreste; Nuñez, Alejandro; Vaquero, Luis; Vegas, Ana María; Crespo, Laura; Fernández-Salazar, Luis; Arranz, Eduardo; Jiménez-García, Victoria Alejandra; Antonio Montes-Cano, Marco; Espín, Beatriz; Galera, Ana; Valverde, Justo; Girón, Francisco José; Bolonio, Miguel; Millán, Antonio; Cerezo, Francesc Martínez; Guajardo, César; Alberto, José Ramón; Rosinach, Mercé; Segura, Verónica; León, Francisco; Marinich, Jorge; Muñoz-Suano, Alba; Romero-Gómez, Manuel; Cebolla, Ángel; Sousa, Carolina

    2016-01-01

    Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. Methods: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Results: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Conclusions: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397. PMID:27644734

  9. Proof test and fatigue crack growth modeling on 2024-T3 aluminum alloy

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr.; Poe, C. C., Jr.; Dawicke, D. S.

    1990-01-01

    Pressure proof testing of aircraft fuselage structures has been suggested as a means of screening critical crack sizes and of extending their useful life. The objective of this paper is to study the proof-test concept and to model the crack-growth process on a ductile material. Simulated proof and operational fatigue life tests have been conducted on cracked panels made of 2024-T3 aluminum alloy sheet material. A fatigue crack-closure model was modified to simulate the proof test and operational fatigue cycling. Using crack-growth rate and resistance-curve data, the model was able to predict crack growth during and after the proof load. These tests and analyses indicate that the proof test increases fatigue life; but the beneficial life, after a 1.33 or 1.5 proof, was less than a few hundred cycles.

  10. Effects of Phenolic Acids on the Growth and Production of T-2 and HT-2 Toxins by Fusarium langsethiae and F. sporotrichioides.

    PubMed

    Ferruz, Elena; Atanasova-Pénichon, Vessela; Bonnin-Verdal, Marie-Noëlle; Marchegay, Gisèle; Pinson-Gadais, Laëtitia; Ducos, Christine; Lorán, Susana; Ariño, Agustín; Barreau, Christian; Richard-Forget, Florence

    2016-04-04

    The effect of natural phenolic acids was tested on the growth and production of T-2 and HT-2 toxins by Fusarium langsethiae and F. sporotrichioides, on Mycotoxin Synthetic medium. Plates treated with 0.5 mM of each phenolic acid (caffeic, chlorogenic, ferulic and p-coumaric) and controls without phenolic acid were incubated for 14 days at 25 °C. Fungal biomass of F. langsethiae and F. sporotrichioides was not reduced by the phenolic acids. However, biosynthesis of T-2 toxin by F. langsethiae was significantly reduced by chlorogenic (23.1%) and ferulic (26.5%) acids. Production of T-2 by F. sporotrichioides also decreased with ferulic acid by 23% (p < 0.05). In contrast, p-coumaric acid significantly stimulated the production of T-2 and HT-2 toxins for both strains. A kinetic study of F. langsethiae with 1 mM ferulic acid showed a significant decrease in fungal biomass, whereas T-2 production increased after 10 days of incubation. The study of gene expression in ferulic supplemented cultures of F. langsethiae revealed a significant inhibition for Tri5, Tri6 and Tri12 genes, while for Tri16 the decrease in gene expression was not statistically significant. Overall, results indicated that phenolic acids had a variable effect on fungal growth and mycotoxin production, depending on the strain and the concentration and type of phenolic acid assayed.

  11. T3 (Triiodothyronine) Test

    MedlinePlus

    ... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

  12. Revealing the Genomic Landscape of Pediatric T-ALL | Office of Cancer Genomics

    Cancer.gov

    T-lineage acute lymphoblastic leukemia (T-ALL) comprises 15-20% of childhood ALL and has historically been associated with inferior outcome to B-cell  ALL (B-ALL). Recent studies have used genome-wide sequencing approaches to identify new subtypes and targets of mutation in B-ALL, but comprehensive sequencing studies of large cohorts of T-ALL have not been performed.

  13. Aptamer redesigned tRNA is nonfunctional and degraded in cells

    PubMed Central

    LEE, DENNIS; MCCLAIN, WILLIAM H.

    2004-01-01

    An RNA aptamer derived from tRNAGln isolated in vitro and a rationally redesigned tRNAGln were used to address the relationship between structure and function of tRNAGln aminoacylation in Escherichia coli. Two mutant tRNAGln sequences were studied: an aptamer that binds 26-fold tighter to glutaminyl-tRNA synthetase than wild-type tRNAGln in vitro, redesigned in the variable loop, and a mutant with near-normal aminoacylation kinetics for glutamine, redesigned to contain a long variable arm. Both mutants were tested in a tRNAGln knockout strain of E. coli, but neither supported knockout cell growth. It was later found that both mutant tRNAs were present in very low amounts in the cell. These results reveal the difference between in vitro and in vivo studies, demonstrating the complexities of in vivo systems that have not been replicated in vitro. PMID:14681579

  14. Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer.

    PubMed

    Wang, Wei-Xin; Lin, Qing-Feng; Shen, Dong; Liu, Shao-Ping; Mao, Wei-Dong; Ma, Gui; Qi, Wei-Dong

    2014-01-01

    Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

  15. Modeling T1 and T2 relaxation in bovine white matter

    NASA Astrophysics Data System (ADS)

    Barta, R.; Kalantari, S.; Laule, C.; Vavasour, I. M.; MacKay, A. L.; Michal, C. A.

    2015-10-01

    The fundamental basis of T1 and T2 contrast in brain MRI is not well understood; recent literature contains conflicting views on the nature of relaxation in white matter (WM). We investigated the effects of inversion pulse bandwidth on measurements of T1 and T2 in WM. Hybrid inversion-recovery/Carr-Purcell-Meiboom-Gill experiments with broad or narrow bandwidth inversion pulses were applied to bovine WM in vitro. Data were analysed with the commonly used 1D-non-negative least squares (NNLS) algorithm, a 2D-NNLS algorithm, and a four-pool model which was based upon microscopically distinguishable WM compartments (myelin non-aqueous protons, myelin water, non-myelin non-aqueous protons and intra/extracellular water) and incorporated magnetization exchange between adjacent compartments. 1D-NNLS showed that different T2 components had different T1 behaviours and yielded dissimilar results for the two inversion conditions. 2D-NNLS revealed significantly more complicated T1/T2 distributions for narrow bandwidth than for broad bandwidth inversion pulses. The four-pool model fits allow physical interpretation of the parameters, fit better than the NNLS techniques, and fits results from both inversion conditions using the same parameters. The results demonstrate that exchange cannot be neglected when analysing experimental inversion recovery data from WM, in part because it can introduce exponential components having negative amplitude coefficients that cannot be correctly modeled with nonnegative fitting techniques. While assignment of an individual T1 to one particular pool is not possible, the results suggest that under carefully controlled experimental conditions the amplitude of an apparent short T1 component might be used to quantify myelin water.

  16. Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response

    PubMed Central

    Feinerman, Ofer; Jentsch, Garrit; Tkach, Karen E; Coward, Jesse W; Hathorn, Matthew M; Sneddon, Michael W; Emonet, Thierry; Smith, Kendall A; Altan-Bonnet, Grégoire

    2010-01-01

    Understanding how the immune system decides between tolerance and activation by antigens requires addressing cytokine regulation as a highly dynamic process. We quantified the dynamics of interleukin-2 (IL-2) signaling in a population of T cells during an immune response by combining in silico modeling and single-cell measurements in vitro. We demonstrate that IL-2 receptor expression levels vary widely among T cells creating a large variability in the ability of the individual cells to consume, produce and participate in IL-2 signaling within the population. Our model reveals that at the population level, these heterogeneous cells are engaged in a tug-of-war for IL-2 between regulatory (Treg) and effector (Teff) T cells, whereby access to IL-2 can either increase the survival of Teff cells or the suppressive capacity of Treg cells. This tug-of-war is the mechanism enforcing, at the systems level, a core function of Treg cells, namely the specific suppression of survival signals for weakly activated Teff cells but not for strongly activated cells. Our integrated model yields quantitative, experimentally validated predictions for the manipulation of Treg suppression. PMID:21119631

  17. Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

    PubMed

    Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

    2013-07-11

    FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

  18. T4 test

    MedlinePlus

    ... Larsen PR, et al, eds. Williams Textbook of Endocrinology . 12th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ... testing. In: Jameson JL, De Groot LJ, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier ...

  19. Methotrimeprazine-induced Corneal Deposits and Cataract Revealed by Urine Drug Profiling Test

    PubMed Central

    Kim, Seong Taeck; Kim, Joon Mo; Kim, Won Young; Choi, Gwang Ju

    2010-01-01

    Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test. PMID:21060765

  20. A Comparison of Two Tests for the Significance of a Mean Vector.

    DTIC Science & Technology

    1978-01-01

    rejected as soon as a component test in the sequence shows significance . It is well. known (3’. Roy 1958; Roy, Gnanadesikan and Srivastava 1971 (p...confidence bounds ” , Annals of Mathematical Statistics, 29, 491—503. (14] Roy, S.N., Gnanadesikan , R., and Srivastava, J.N. (1971). Analysis and

  1. Initial test of a T9-like P300-based speller by an ALS patient

    NASA Astrophysics Data System (ADS)

    Ron-Angevin, R.; Varona-Moya, S.; da Silva-Sauer, L.

    2015-08-01

    Objective. Visual P300-based brain-computer interface spellers offer a useful communication channel for locked-in patients, who are completely dependent in their daily lives. One of the research goals for these systems is to achieve greater communication rates by means of modifying some features of their interfaces, e.g., reducing the matrix size. However, such modifications may not work well with disabled end-users, such as patients of amyotrophic lateral sclerosis (ALS), due to a supposed reduction of their cognitive resources. The purpose of the present study was to provide a proof of concept that ALS patients could efficiently use a P300-based speller with a 4 × 3 symbol matrix based on the T9 interface developed for mobile phones. Approach. We conducted an experiment with a sample of 11 able-bodied participants and one locked-in patient with ALS. All participants tested our T9-like visual P300-based speller and also two different 7 × 6 matrix spellers based on Farwell and Donchin’s classic proposal—one of them included a word predictor system like the T9-like speller did. Main results. The performance analyses indicated that the locked-in patient benefited from using a reduced matrix size as much as healthy users did, spelling words almost 1.6 times faster and equally accurately when using the T9-like speller than when using the alternative spellers. Significance. Due to counting on only one locked-in patient, the current work constitutes a feasibility study. The actual usability of systems such as the one proposed in this paper should be determined by means of studies with a greater number of end-users in real-life conditions.

  2. The Building Blocks for JWST I and T (Integrations and Test) to Operations - From Simulator to Flight Units

    NASA Technical Reports Server (NTRS)

    Fatig, Curtis; Ochs, William; Johns, Alan; Seaton, Bonita; Adams, Cynthia; Wasiak, Francis; Jones, Ronald; Jackson, Wallace

    2012-01-01

    The James Webb Space Telescope (JWST) Project has an extended integration and test (I&T) phase due to long procurement and development times of various components as well as recent launch delays. The JWST Ground Segment and Operations group has developed a roadmap of the various ground and flight elements and their use in the various JWST I&T test programs. The JWST Project s building block approach to the eventual operational systems, while not new, is complex and challenging; a large-scale mission like JWST involves international partners, many vendors across the United States, and competing needs for the same systems. One of the challenges is resource balancing so simulators and flight products for various elements congeal into integrated systems used for I&T and flight operations activities. This building block approach to an incremental buildup provides for early problem identification with simulators and exercises the flight operations systems, products, and interfaces during the JWST I&T test programs. The JWST Project has completed some early I&T with the simulators, engineering models and some components of the operational ground system. The JWST Project is testing the various flight units as they are delivered and will continue to do so for the entire flight and operational system. The JWST Project has already and will continue to reap the value of the building block approach on the road to launch and flight operations.

  3. Comparison of two anaerobic water polo-specific tests with the Wingate test.

    PubMed

    Bampouras, Theodoros M; Marrin, Kelly

    2009-01-01

    The purpose of the current study was to compare 2 water polo-specific tests-the 14 x 25-m swims (SWIM) and the 30-second crossbar jumps (30CJ)-with a laboratory-based test of anaerobic power, the Wingate Anaerobic Test (WAnT). Thirteen elite women's water polo players (mean +/- SD: age 22.0 +/- 4.4 years, height 168.7 +/- 7.9 cm, body mass 65.9 +/- 6.1 kg, body fat 23.6 +/- 3.5 %, maximum oxygen uptake 51.4 +/- 4.5 mlxkgxmin) participated in the study. The SWIM involved 14 repeated "all-out" sprints every 30 seconds. Swimming time was recorded, and sprint velocity, mean velocity (Vmean), and the gradient of the linear regression equation (GRADIENT) were calculated. The 30CJ involved repeated in-water water polo jumps and touching the goal crossbar with both hands. The number of touches in 30 seconds was recorded. Additionally, the subjects completed a 30-second WAnT, and mean power (Mp) and fatigue index (FI) were calculated. Kendall tau (tau) rank correlation was used to examine for correlation between ranks. Significance level was set at p significant correlation was found between any of the measures of the WAnT and the 2 sport-specific tests. It was suggested that the WAnT may not be an appropriate evaluation tool for anaerobic power assessment of water polo players, stressing the importance of sport-specific tests.

  4. Integrated genomic and immunophenotypic classification of pancreatic cancer reveals three distinct subtypes with prognostic/predictive significance.

    PubMed

    Wartenberg, Martin; Cibin, Silvia; Zlobec, Inti; Vassella, Erik; Eppenberger-Castori, Serenella M M; Terracciano, Luigi; Eichmann, Micha; Worni, Mathias; Gloor, Beat; Perren, Aurel; Karamitopoulou, Eva

    2018-04-16

    Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins. Previous data on FOXP3 were integrated. Immune-cell counts and protein expression were correlated with tumor-derived driver mutations, clinicopathologic features (TNM 8. 2017), survival and epithelial-mesenchymal-transition (EMT)-like tumor budding.  Results: Three PDAC-subtypes were identified: the "immune-escape" (54%), poor in T- and B-cells and enriched in FOXP3+Tregs, with high-grade budding, frequent CDKN2A- , SMAD4- and PIK3CA-mutations and poor outcome; the "immune-rich" (35%), rich in T- and B-cells and poorer in FOXP3+Tregs, with infrequent budding, lower CDKN2A- and PIK3CA-mutation rate and better outcome and a subpopulation with tertiary lymphoid tissue (TLT), mutations in DNA damage response genes (STK11, ATM) and the best outcome; and the "immune-exhausted" (11%) with immunogenic microenvironment and two subpopulations: one with PD-L1-expression and high PIK3CA-mutation rate and a microsatellite-unstable subpopulation with high prevalence of JAK3-mutations. The combination of low budding, low stromal FOXP3-counts, presence of TLTs and absence of CDKN2A-mutations confers significant survival advantage in PDAC-patients. Immune host responses correlate with tumor characteristics leading to morphologically recognizable PDAC-subtypes with prognostic/predictive significance. Copyright ©2018

  5. Company fires worker after test reveals AIDS drug in his blood.

    PubMed

    1996-02-09

    [Name removed], a vitamin and herbal supplement manufacturer, claims that it terminated [name removed] because of the presence of a cannabinoid in his blood, not because he has AIDS. A random drug test revealed that Mr. [Name removed], a quality control inspector, had Marinol in his blood, a medication prescribed to enhance appetite. [Name removed]'s AIDS status was revealed when [name removed]'s physician proved that the prescription was legitimate. Solaray's policy allows AIDS patients to continue working as long as they meet acceptable performance standards. The American Civil Liberties Union Foundation of Utah filed suit on [name removed]'s behalf. Concomitantly, the U.S. Equal Employment Opportunity Commission (EEOC) concluded that [name removed] violates the Americans with Disabilities Act (ADA) by demanding medical records and forcing workers to undergo periodic medical exams. [Name removed] justifies its demand by citing an obligation to protect all employees, customers, and other visitors. [Name removed] has refused to settle out of court or to allow [name removed] to return to work. The company contends that Marinol, a psychoactive substance, negatively affects [name removed]'s ability to perform quality control tasks. Attorneys for [name removed] will begin the deposition process in February 1996.

  6. Implementation of Point-of-Care Diagnostics Leads to Variable Uptake of Syphilis, Anemia and CD4+ T-Cell Count Testing in Rural Maternal and Child Health Clinics.

    PubMed

    De Schacht, Caroline; Lucas, Carlota; Sitoe, Nádia; Machekano, Rhoderick; Chongo, Patrina; Temmerman, Marleen; Tobaiwa, Ocean; Guay, Laura; Kassaye, Seble; Jani, Ilesh V

    2015-01-01

    Anemia, syphilis and HIV are high burden diseases among pregnant women in sub-Saharan Africa. A quasi-experimental study was conducted in four health facilities in Southern Mozambique to evaluate the effect of point-of-care technologies for hemoglobin quantification, syphilis testing and CD4+ T-cell enumeration performed within maternal and child health services on testing and treatment coverage, and assessing acceptability by health workers. Demographic and testing data on women attending first antenatal care services were extracted from existing records, before (2011; n = 865) and after (2012; n = 808) introduction of point-of-care testing. Study outcomes per health facility were compared using z-tests (categorical variables) and Wilcoxon rank-sum test (continuous variables), while inverse variance weights were used to adjust for possible cluster effects in the pooled analysis. A structured acceptability-assessment interview was conducted with health workers before (n = 22) and after (n = 19). After implementation of point-of-care testing, there was no significant change in uptake of overall hemoglobin screening (67.9% to 83.0%; p = 0.229), syphilis screening (80.8% to 87.0%; p = 0.282) and CD4+ T-cell testing (84.9% to 83.5%; p = 0.930). Initiation of antiretroviral therapy for treatment eligible women was similar in the weighted analysis before and after, with variability among the sites. Time from HIV diagnosis to treatment initiation decreased (median of 44 days to 17 days; p<0.0001). A generally good acceptability for point-of-care testing was seen among health workers. Point-of-care CD4+ T-cell enumeration resulted in a decreased time to initiation of antiretroviral therapy among treatment eligible women, without significant increase in testing coverage. Overall hemoglobin and syphilis screening increased. Despite the perception that point-of-care technologies increase access to health services, the variability in results indicate the potential for

  7. High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires.

    PubMed

    Liaskou, Evaggelia; Klemsdal Henriksen, Eva Kristine; Holm, Kristian; Kaveh, Fatemeh; Hamm, David; Fear, Janine; Viken, Marte K; Hov, Johannes Roksund; Melum, Espen; Robins, Harlan; Olweus, Johanna; Karlsen, Tom H; Hirschfield, Gideon M

    2016-05-01

    Hepatic T-cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune-mediated liver diseases. Conceptually the presence of disease-associated antigens is predicted to be reflected in T-cell receptor (TCR) repertoires. Here, we aimed to determine if disease-associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high-throughput sequencing of the TCRβ chain complementarity-determining region 3 of liver-infiltrating T cells from PSC (n = 20), PBC (n = 10), and ALD (n = 10) patients, alongside genomic human leukocyte antigen typing. The frequency of TCRβ nucleotide sequences was significantly higher in PSC samples (2.53 ± 0.80, mean ± standard error of the mean) compared to PBC samples (1.13 ± 0.17, P < 0.0001) and ALD samples (0.62 ± 0.10, P < 0.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (P = 0.024) and ALD groups (0.40%, P < 0.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (≥30% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen-driven selection. In PSC and PBC, disease-associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. We demonstrate liver-infiltrating disease-associated clonotypes in all three diseases evaluated, and evidence for antigen-driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high-throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases

  8. Correlation between thyroidal and peripheral blood total T cells, CD8+ T cells, and CD8+ T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves' ophthalmopathy.

    PubMed

    Al-Ansari, Farah; Lahooti, Hooshang; Stokes, Leanne; Edirimanne, Senarath; Wall, Jack

    2018-05-22

    Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 +  T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO. Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method. We found a positive correlation between thyroidal CD8 +  T cells and CD8 +  T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII. Our observations provide further evidence for a possible role of thyroidal CD8 +  T cells, CD8 +  T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.

  9. A novel measure and significance testing in data analysis of cell image segmentation.

    PubMed

    Wu, Jin Chu; Halter, Michael; Kacker, Raghu N; Elliott, John T; Plant, Anne L

    2017-03-14

    Cell image segmentation (CIS) is an essential part of quantitative imaging of biological cells. Designing a performance measure and conducting significance testing are critical for evaluating and comparing the CIS algorithms for image-based cell assays in cytometry. Many measures and methods have been proposed and implemented to evaluate segmentation methods. However, computing the standard errors (SE) of the measures and their correlation coefficient is not described, and thus the statistical significance of performance differences between CIS algorithms cannot be assessed. We propose the total error rate (TER), a novel performance measure for segmenting all cells in the supervised evaluation. The TER statistically aggregates all misclassification error rates (MER) by taking cell sizes as weights. The MERs are for segmenting each single cell in the population. The TER is fully supported by the pairwise comparisons of MERs using 106 manually segmented ground-truth cells with different sizes and seven CIS algorithms taken from ImageJ. Further, the SE and 95% confidence interval (CI) of TER are computed based on the SE of MER that is calculated using the bootstrap method. An algorithm for computing the correlation coefficient of TERs between two CIS algorithms is also provided. Hence, the 95% CI error bars can be used to classify CIS algorithms. The SEs of TERs and their correlation coefficient can be employed to conduct the hypothesis testing, while the CIs overlap, to determine the statistical significance of the performance differences between CIS algorithms. A novel measure TER of CIS is proposed. The TER's SEs and correlation coefficient are computed. Thereafter, CIS algorithms can be evaluated and compared statistically by conducting the significance testing.

  10. Comparison of ventilation threshold and heart rate deflection point in fast and standard treadmill test protocols.

    PubMed

    Vucetić, Vlatko; Sentija, Davor; Sporis, Goran; Trajković, Nebojsa; Milanović, Zoran

    2014-06-01

    The purpose of this study was to compare two methods for determination of anaerobic threshold from two different treadmill protocols. Forty-eight Croatian runners of national rank (ten sprinters, fifteen 400-m runners, ten middle distance runners and thirteen long distance runners), mean age 21.7 +/- 5.1 years, participated in the study. They performed two graded maximal exercise tests on a treadmill, a standard ramp treadmill test (T(SR), speed increments of 1 km x h(-1) every 60 seconds) and a fast ramp treadmill test (T(FR), speed increments of 1 km x h(-1) every 30 seconds) to determine and compare the parameters at peak values and at heart rate at the deflection point (HR(DP)) and ventilation threshold (VT). There were no significant differences between protocols (p > 0.05) for peak values of oxygen uptake (VO(2max), 4.48 +/- 0.43 and 4.44 +/- 0.45 L x min(-1)), weight related VO(2max) (62.5 +/- 6.2 and 62.0 +/- 6.0 mL x kg(-1) x min(-1)), pulmonary ventilation (VE(max), 163.1 +/- 18.7 and 161.3 +/- 19.9 L x min(-1)) and heart rate (HR(max), 192.3 +/- 8.5 and 194.4 +/- 8.7 bpm) (T(FR) and T(SR), respectively). Moreover, no significant differences between T(FR) and T(SR) where found for VT and HR(DP) when expressed as VO2 and HR. However, there was a significant effect of ramp slope on running speed at VO(2max) and at the anaerobic threshold (AnT), independent of the method used (VT: 16.0 +/- 2.2 vs 14.9 +/- 2.2 km x h(-1);HR(DP): 16.5 +/- 1.9 vs 14.9 +/- 2.0 km x h(-1) for T(FR) and T(SR) respectively). Linear regression analysis revealed high between-test and between-method correlations for VO2, HR and running speed parameters (r = 0.78-0.89, p < 0.01). The present study has indicated that the VT and HR(DP) for running (VO2, ventilation, and heart rate at VT/HR(DP)) are independent of test protocol, while there is a significant effect of ramp slope on VT and HR(DP) when expressed as running speed. Moreover, this study demonstrates that the point of deflection

  11. Antimicrobial Activity and Chemical Composition of “Kpètè-Kpètè”: A Starter of Benin Traditional Beer Tchoukoutou

    PubMed Central

    N'tcha, Christine; Sina, Haziz; Kayodé, Adéchola Pierre Polycarpe; Gbenou, Joachim D.

    2017-01-01

    The aim of this study was to investigate the antibacterial effect of the crude starter “kpètè-kpètè” and lactic acid bacteria used during the production of “tchoukoutou.” To achieve this, a total of 11 lactic acid bacteria and 40 starter samples were collected from four communes. The samples were tested on 29 gram + and − strains by disk diffusion method. The minimum inhibitory and bactericidal concentrations of starter and lactic acid bacteria were determined by conventional methods. Organic acids, sugar, and volatile compounds were determined using the HPLC method. The “kpètè-kpètè” displays a high antibacterial activity against the tested strains. The most sensitive strain was S. epidermidis (12.5 mm) whereas the resistance strain was Proteus mirabilis (8 mm). All the tested ferment has not any inhibitory effect on Enterococcus faecalis. The lactic acid bacteria isolates of Parakou showed the highest (17.48 mm) antibacterial activity whereas the smallest diameter was obtained with the ferment collected from Boukoumbé (9.80 mm). The starters' chemical screening revealed the presence of tannins, anthocyanin flavonoids, triterpenes, steroids, reducing compounds, and mucilage O-glycosides. These compounds are probably the source of recorded inhibition effect. The lactic acid bacteria of the “kpètè-kpètè” could be used to develop a food ingredient with probiotic property. PMID:28367445

  12. Residual pathological stage at radical cystectomy significantly impacts outcomes for initial T2N0 bladder cancer.

    PubMed

    Isbarn, Hendrik; Karakiewicz, Pierre I; Shariat, Shahrokh F; Capitanio, Umberto; Palapattu, Ganesh S; Sagalowsky, Arthur I; Lotan, Yair; Schoenberg, Mark P; Amiel, Gilad E; Lerner, Seth P; Sonpavde, Guru

    2009-08-01

    We hypothesized that in patients with T2N0 stage disease at transurethral bladder tumor resection a lower residual cancer stage (P1N0 or less) at radical cystectomy may correlate with improved outcomes relative to those with residual P2N0 disease. We analyzed 208 patients with T2N0 stage disease at transurethral bladder tumor resection whose tumors were organ confined at radical cystectomy (P2 or lower, pN0). None received perioperative chemotherapy. Kaplan-Meier as well as univariable and multivariable Cox regression models addressed the effect of residual pT stage at radical cystectomy on recurrence and cancer specific mortality rates. Covariates consisted of age, gender, grade, lymphovascular invasion, carcinoma in situ, number of lymph nodes removed and year of surgery. Residual pT stage at radical cystectomy was P0 in 24 (11.5%) patients, Pa in 9 (4.3%), PCIS in 22 (10.6%), P1 in 35 (16.8%) and P2 in 118 (56.7%). Median followup of censored patients was 55.7 months for recurrence and 52.1 months for cancer specific mortality analyses. The 5-year recurrence-free survival rates of patients with P0/Pa/PCIS, P1 and P2 stage disease were 100%, 85% and 75%, respectively. The 5-year cancer specific survival rates for the same cohorts were 100%, 93% and 81%, respectively. On multivariable analysis the effect of residual stage P1 or lower at radical cystectomy achieved independent predictor status for recurrence (adjusted HR 0.20, p = 0.002) and cancer specific mortality (adjusted HR 0.24, p = 0.02). Down staging from initial T2N0 bladder cancer at transurethral bladder tumor resection to lower stage at radical cystectomy significantly reduces recurrence and cancer specific mortality. Further validation of this finding is warranted.

  13. Multicolor flow-cytometric analysis of milk allergen-specific T-helper type 2 cells revealed coexpression of interleukin-4 with Foxp3.

    PubMed

    Yamawaki, Kazuo; Inuo, Chisato; Nomura, Takayasu; Tanaka, Kenichi; Nakajima, Yoichi; Kondo, Yasuto; Yoshikawa, Tetsushi; Urisu, Atsuo; Tsuge, Ikuya

    2015-12-01

    Allergen-specific T-helper type 2 (TH2) cells play an important role in the development of allergic inflammation; however, investigations of the properties of allergen-specific T cells have been challenging in humans. Despite clear evidence that forkhead box p3 (Foxp3) is expressed in conventional effector T cells, its function has remained unknown. To characterize allergen-specific TH2 cells in milk allergy, with particular focus on the expression of Foxp3. Twenty-one children with milk allergy and 11 children without milk allergy were studied. Peripheral blood mononuclear cells from subjects were stimulated with milk allergen for 6 hours and analyzed using multicolor flow cytometry to identify CD154(+) allergen-specific T-helper cells. Simultaneously, the expression of intracellular cytokines and Foxp3 was analyzed. The milk allergy group had significantly larger numbers of milk allergen-specific interleukin (IL)-4- and IL-5-producing CD4(+) T cells than the control group. Subjects in the milk allergy group had significantly more CD154(+)CD4(+) IL-10-producing cells and CD154(+)Foxp3(+)CD4(+) cells than those in the control group. In addition, the number of milk allergen-specific CD154(+)Foxp3(+)CD4(+) cells strongly correlated with that of CD154(+)IL4(+)CD4(+) cells. Bcl-2 expression in CD154(+)IL-4(+)Foxp3(+) T-helper cells was significantly lower compared with that in total CD4 cells. Increased numbers of IL-4-producing allergen-specific T-helper cells were found in patients with milk allergy. In addition, Foxp3 was coexpressed with IL-4 in allergen-specific TH2 cells from patients. This coexpression was associated with lower Bcl-2 levels and could contribute to the phenotype and function of TH2 cells. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. f(T,T) gravity and cosmology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harko, Tiberiu; Lobo, Francisco S.N.; Otalora, G.

    2014-12-01

    We present an extension of f(T) gravity, allowing for a general coupling of the torsion scalar T with the trace of the matter energy-momentum tensor T. The resulting f(T,T) theory is a new modified gravity, since it is different from all the existing torsion or curvature based constructions. Applied to a cosmological framework, it leads to interesting phenomenology. In particular, one can obtain a unified description of the initial inflationary phase, the subsequent non-accelerating, matter-dominated expansion, and then the transition to a late-time accelerating phase. Additionally, the effective dark energy sector can be quintessence or phantom-like, or exhibit the phantom-dividemore » crossing during the evolution. Moreover, in the far future the universe results either to a de Sitter exponential expansion, or to eternal power-law accelerated expansions. Finally, a detailed study of the scalar perturbations at the linear level reveals that f(T,T) cosmology can be free of ghosts and instabilities for a wide class of ansatzes and model parameters.« less

  15. Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.

    PubMed

    Karur, Gauri R; Robison, Sean; Iwanochko, Robert M; Morel, Chantal F; Crean, Andrew M; Thavendiranathan, Paaladinesh; Nguyen, Elsie T; Mathur, Shobhit; Wasim, Syed; Hanneman, Kate

    2018-04-24

    Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P < .001]; 1192 msec ± 52 vs 1268 msec ± 55 [P < .001]; and 1221 msec ± 54 vs 1271 msec ± 37 [P = .001], respectively). A septal LV native T1 cutoff point of 1220 msec or lower distinguished AFD from HCM with sensitivity of 97%, specificity of 93%, and accuracy of 95%. Septal LV native T1 values differentiated AFD from HCM after adjustment for age, sex, and conventional imaging features (odds ratio, 0.94; 95% confidence interval: 0.91, 0.98; P = < .001). In a nested logistic regression model with age, sex, and conventional imaging features, model fit was significantly improved by the addition of septal LV native T1 values (χ 2 [df = 1] = 33.4; P < .001). Conclusion Cardiac MR imaging native T1 values at 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic

  16. Measured dose to ovaries and testes from Hodgkin's fields and determination of genetically significant dose

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Niroomand-Rad, A.; Cumberlin, R.

    The purpose of this study was to determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm[sup 3] dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. The results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimatedmore » doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. 28 refs., 3 figs., 5 tabs.« less

  17. DarT: The embryo test with the Zebrafish Danio rerio--a general model in ecotoxicology and toxicology.

    PubMed

    Nagel, Roland

    2002-01-01

    The acute fish test is an animal test whose ecotoxicological relevance is worthy of discussion. The primary aim of protection in ecotoxicology is the population and not the individual. Furthermore the concentration of pollutants in the environment is normally not in the lethal range. Therefore the acute fish test covers solely the situation after chemical spills. Nevertheless, acute fish toxicity data still belong to the base set used for the assessment of chemicals. The embryo test with the zebrafish Danio rerio (DarT) is recommended as a substitute for the acute fish test. For validation an international laboratory comparison test was carried out. A summary of the results is presented in this paper. Based on the promising results of testing chemicals and waste water the test design was validated by the DIN-working group "7.6 Fischei-Test". A normed test guideline for testing waste water with fish is available. The test duration is short (48 h) and within the test different toxicological endpoints can be examined. Endpoints from the embryo test are suitable for QSAR-studies. Besides the use in ecotoxicology the introduction as a toxicological model was investigated. Disturbance of pigmentation and effects on the frequency of heart-beat were examined. A further important application is testing of teratogenic chemicals. Based on the results DarT could be a screening test within preclinical studies.

  18. Material testing of reconditioned orthodontic brackets.

    PubMed

    Reimann, S; Rewari, A; Keilig, L; Widu, F; Jäger, A; Bourauel, C

    2012-12-01

    While all manufacturers of orthodontic brackets label these products for single use, there are commercial providers offering bracket reconditioning (or "recycling"). We conducted this study to investigate the effects of different recycling techniques on material-related parameters in orthodontic brackets, aiming to derive indications for clinical use and conclusions about the biocompatibility, longevity, and application of recycled brackets. New metal brackets (equilibrium(®); Dentaurum, Ispringen, Germany) were compared to brackets recycled by different techniques, including direct flaming with a Bunsen burner, chemical reconditioning in an acid bath, a commercial unit (Big Jane; Esmadent, IL, USA), and outsourcing to a company (Ortho Clean, Dellstedt, Germany). Material-related examinations included the following: (1) corrosion behavior by static immersion testing and use of a mass spectrometer to determine nickel-ion concentrations in the corrosive medium, (2) surface features in scanning electron micrographs before and after corrosion testing, (3) Vickers hardness using a hardness testing machine, (4) shear bond strength as defined in DIN 13990-1, (5) dimensional stability of the bracket slots by light microscopy, and (6) frictional loss as assessed by an orthodontic measurement and simulation system (OMSS). Each examination was performed on ten brackets. Student's t-test was used for statistical analysis. Compared to the new brackets, those recycled in an acid bath or by a commercial provider revealed significant dimensional changes (p<0.05). Corrosion on the recycled brackets varied according to the recycling techniques employed. The group of brackets recycled by one company revealed hardness values that differed from those of all the other groups. No significant differences were observed in nickel-ion release, frictional loss, and shear bond strength. Recycling was found to significantly reduce the corrosion resistance and dimensional stability of

  19. Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

    PubMed Central

    Christofferson, Austin; Aldrich, Jessica; Jewell, Scott; Kittles, Rick A.; Derome, Mary; Craig, David Wesley; Carpten, John D.

    2017-01-01

    Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups. Of interest, BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations. PMID:29166413

  20. Torsion Tests of 24S-T Aluminum-alloy Noncircular Bar and Tubing

    NASA Technical Reports Server (NTRS)

    Moore, R L; Paul, D A

    1943-01-01

    Tests of 24S-T aluminum alloy have been made to determine the yield and ultimate strengths in torsion of noncircular bar and tubing. An approximate basis for predicting these torsional strength characteristics has been indicated. The results show that the torsional stiffness and maximum shearing stresses within the elastic range may be computed quite closely by means of existing formulas based on mathematical analysis and the membrane analogy.

  1. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    PubMed

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-07

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

  2. Use of power analysis to develop detectable significance criteria for sea urchin toxicity tests

    USGS Publications Warehouse

    Carr, R.S.; Biedenbach, J.M.

    1999-01-01

    When sufficient data are available, the statistical power of a test can be determined using power analysis procedures. The term “detectable significance” has been coined to refer to this criterion based on power analysis and past performance of a test. This power analysis procedure has been performed with sea urchin (Arbacia punctulata) fertilization and embryological development data from sediment porewater toxicity tests. Data from 3100 and 2295 tests for the fertilization and embryological development tests, respectively, were used to calculate the criteria and regression equations describing the power curves. Using Dunnett's test, a minimum significant difference (MSD) (β = 0.05) of 15.5% and 19% for the fertilization test, and 16.4% and 20.6% for the embryological development test, for α ≤ 0.05 and α ≤ 0.01, respectively, were determined. The use of this second criterion reduces type I (false positive) errors and helps to establish a critical level of difference based on the past performance of the test.

  3. Immunoglobulin Tau Heavy Chain (IgT) in Flounder, Paralichthys olivaceus: Molecular Cloning, Characterization, and Expression Analyses

    PubMed Central

    Du, Yang; Tang, Xiaoqian; Zhan, Wenbin; Xing, Jing; Sheng, Xiuzhen

    2016-01-01

    Immunoglobulin tau (IgT) is a new teleost immunoglobulin isotype, and its potential function in adaptive immunity is not very clear. In the present study, the membrane-bound and secreted IgT (mIgT and sIgT) heavy chain genes were cloned for the first time and characterized in flounder (Paralichthys olivaceus), and found the nucleic acid sequence were exactly same in the Cτ1–Cτ4 constant domains of mIgT and sIgT, but different in variable regions and the C-terminus. The amino acid sequence of mIgT shared higher similarity with Bovichtus diacanthus (51.2%) and Dicentrarchus labrax (45.0%). Amino acid of flounder IgT, IgM, and IgD heavy chain was compared and the highest similarity was found between IgT Cτ1 and IgM Cμ1 (38%). In healthy flounder, the transcript levels of IgT mRNA were the highest in gill, spleen, and liver, and higher in peripheral blood leucocytes, skin, and hindgut. After infection and vaccination with Edwardsiella tarda via intraperitoneal injection and immersion, the qRT-PCR analysis demonstrated that the IgT mRNA level was significantly upregulated in all tested tissues, with similar dynamic tendency that increased firstly and then decreased, and higher in gill, skin, hindgut, liver, and stomach in immersion than in the injection group, but no significant difference existed in spleen and head kidney between immersion and injection groups. These results revealed that IgT responses could be simultaneously induced in both mucosal and systemic tissues after infection/vaccination via injection and immersion route, but IgT might play a more important role in mucosal immunity than in systemic immunity. PMID:27649168

  4. Development of an antibody to bovine IL-2 reveals multifunctional CD4 T(EM) cells in cattle naturally infected with bovine tuberculosis.

    PubMed

    Whelan, Adam O; Villarreal-Ramos, Bernardo; Vordermeier, H Martin; Hogarth, Philip J

    2011-01-01

    Gaining a better understanding of the T cell mechanisms underlying natural immunity to bovine tuberculosis would help to identify immune correlates of disease progression and facilitate the rational design of improved vaccine and diagnostic strategies. CD4 T cells play an established central role in immunity to TB, and recent interest has focussed on the potential role of multifunctional CD4 T cells expressing IFN-γ, IL-2 and TNF-α. Until now, it has not been possible to assess the contribution of these multifunctional CD4 T cells in cattle due to the lack of reagents to detect bovine IL-2 (bIL-2). Using recombinant phage display technology, we have identified an antibody that recognises biologically active bIL-2. Using this antibody, we have developed a polychromatic flow cytometric staining panel that has allowed the investigation of multifunctional CD4 T-cells responses in cattle naturally infected with M. bovis. Assessment of the frequency of antigen specific CD4 T cell subsets reveals a dominant IFN-γ(+)IL-2(+)TNF-α(+) and IFN-γ(+) TNF-α(+) response in naturally infected cattle. These multifunctional CD4 T cells express a CD44(hi)CD45RO(+)CD62L(lo) T-effector memory (T(EM)) phenotype and display higher cytokine median fluorescence intensities than single cytokine producers, consistent with an enhanced 'quality of response' as reported for multifunctional cells in human and murine systems. Through our development of these novel immunological bovine tools, we provide the first description of multifunctional T(EM) cells in cattle. Application of these tools will improve our understanding of protective immunity in bovine TB and allow more direct comparisons of the complex T cell mediated immune responses between murine models, human clinical studies and bovine TB models in the future. © 2011 Whelan et al.

  5. 3D reconstruction of the Shigella T3SS transmembrane regions reveals 12-fold symmetry and novel features throughout

    PubMed Central

    Hodgkinson, Julie L.; Horsley, Ashley; Stabat, David; Simon, Martha; Johnson, Steven; da Fonseca, Paula C. A.; Morris, Edward P.; Wall, Joseph S.; Lea, Susan M.; Blocker, Ariel J.

    2009-01-01

    Type III secretion systems (T3SSs) mediate bacterial protein translocation into eukaryotic cells, a process essential for virulence of many Gram-negative pathogens. They are composed of a cytoplasmic secretion machinery and a base bridging both bacterial membranes into which a hollow, external needle is embedded. When isolated, the latter two parts are termed ‘needle complex’ (NC). Incomplete understanding of NC structure hampers studies of T3SS function. To estimate the stoichiometry of its components, the mass f its sub-domains was measured by scanning transmission electron microscopy (STEM). Subunit symmetries were determined by analysis of top and side views within negatively stained samples in low dose transmission electron microscopy (TEM). Application of 12-fold symmetry allowed generation of a 21-25Å resolution three-dimensional (3D) reconstruction of the NC base, revealing many new features and permitting tentative docking of the crystal structure of EscJ, an inner membrane component. PMID:19396171

  6. Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter Zell (left) and Dr Clifton Horne (right) are shown preparing a laser light sheet for a flow visualization test. Shown standing in the nacelle of the ADP is John Girvin, senior test engineer for Pratt & Whitney.

  7. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    PubMed

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (p<2.2e-16) than HK gene promoters. The entropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis

    PubMed Central

    2014-01-01

    Background There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB. Methods This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months. Results There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months. Conclusions We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests. PMID:24904240

  9. New computational methods reveal tRNA identity element divergence between Proteobacteria and Cyanobacteria.

    PubMed

    Freyhult, Eva; Cui, Yuanyuan; Nilsson, Olle; Ardell, David H

    2007-10-01

    There are at least 21 subfunctional classes of tRNAs in most cells that, despite a very highly conserved and compact common structure, must interact specifically with different cliques of proteins or cause grave organismal consequences. Protein recognition of specific tRNA substrates is achieved in part through class-restricted tRNA features called tRNA identity determinants. In earlier work we used TFAM, a statistical classifier of tRNA function, to show evidence of unexpectedly large diversity among bacteria in tRNA identity determinants. We also created a data reduction technique called function logos to visualize identity determinants for a given taxon. Here we show evidence that determinants for lysylated isoleucine tRNAs are not the same in Proteobacteria as in other bacterial groups including the Cyanobacteria. Consistent with this, the lysylating biosynthetic enzyme TilS lacks a C-terminal domain in Cyanobacteria that is present in Proteobacteria. We present here, using function logos, a map estimating all potential identity determinants generally operational in Cyanobacteria and Proteobacteria. To further isolate the differences in potential tRNA identity determinants between Proteobacteria and Cyanobacteria, we created two new data reduction visualizations to contrast sequence and function logos between two taxa. One, called Information Difference logos (ID logos), shows the evolutionary gain or retention of functional information associated to features in one lineage. The other, Kullback-Leibler divergence Difference logos (KLD logos), shows recruitments or shifts in the functional associations of features, especially those informative in both lineages. We used these new logos to specifically isolate and visualize the differences in potential tRNA identity determinants between Proteobacteria and Cyanobacteria. Our graphical results point to numerous differences in potential tRNA identity determinants between these groups. Although more differences in

  10. The Human SepSecS-tRNASec Complex Reveals the Mechanism of Selenocysteine Formation

    PubMed Central

    Palioura, Sotiria; Sherrer, R. Lynn; Steitz, Thomas A.; Söll, Dieter; Simonović, Miljan

    2010-01-01

    Selenocysteine is the only genetically encoded amino acid in humans whose biosynthesis occurs on its cognate transfer RNA (tRNA). O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) catalyzes the final step of selenocysteine formation by a poorly understood tRNA-dependent mechanism. The crystal structure of human tRNASec in complex with SepSecS, phosphoserine, and thiophosphate, together with in vivo and in vitro enzyme assays, supports a pyridoxal phosphate–dependent mechanism of Sec-tRNASec formation. Two tRNASec molecules, with a fold distinct from other canonical tRNAs, bind to each SepSecS tetramer through their 13–base pair acceptor-TΨC arm (where Ψ indicates pseudouridine). The tRNA binding is likely to induce a conformational change in the enzyme’s active site that allows a phosphoserine covalently attached to tRNASec, but not free phosphoserine, to be oriented properly for the reaction to occur. PMID:19608919

  11. [Extranodal nasal type NK/T-cell lymphoma: the expression of Epstein-Barr virus latent membrane protein 1 and its significance of prognosis].

    PubMed

    Zhao, Sha; Liu, Wei-ping; Zhang, Wen-yan; Li, Gan-di

    2005-05-01

    To investigate the expression and prognostic significance of Epstein-Barr virus latent membrane protein 1 in extranodal nasal type NK/T-cell lymphoma in the Chengdu area. The expression of latent membrane protein-1 (LMP1) was detected by immunohistochemistry (IHC) and DNA-PCR in 67 cases of extranodal nasal type NK/T-cell lymphoma, and the differences in survival rate between positive and negative expression groups of LMP1-protien and LMP1-DNA were analyzed respectively. Ten (14.93%) cases were positive at LMP1-protein level, and fifty-six (83.58%) were positive at LMP1-DNA level. The total expression rate of LMP1 was 83.58%. No statistically significant difference was observed between the expression of LMP1 and prognosis (P = 0.678) and between the expression of LMP1-DNA and prognosis (P = 0.943). LMP1 was shown to be closely associated with extranodal nasal type NK/T-cell lymphoma in Chengdu. The expression rate of LMP1 at protein level was different from that at DNA level. No relationship was found between the prognosis and the LMP1 expression in extranodal nasal type NK/T-cell lymphoma.

  12. DIRECT SPECTRUM OF THE BENCHMARK T DWARF HD 19467 B

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crepp, Justin R.; Matthews, Christopher T.; Rice, Emily L.

    2015-01-10

    HD 19467 B is presently the only directly imaged T dwarf companion known to induce a measurable Doppler acceleration around a solar-type star. We present spectroscopy measurements of this important benchmark object taken with the Project 1640 integral field unit at Palomar Observatory. Our high-contrast R ≈ 30 observations obtained simultaneously across the JH bands confirm the cold nature of the companion as reported from the discovery article and determine its spectral type for the first time. Fitting the measured spectral energy distribution to SpeX/IRTF T dwarf standards and synthetic spectra from BT-Settl atmospheric models, we find that HD 19467 B is a T5.5more » ± 1 dwarf with effective temperature T{sub eff}=978{sub −43}{sup +20} K. Our observations reveal significant methane absorption affirming its substellar nature. HD 19467 B shows promise to become the first T dwarf that simultaneously reveals its mass, age, and metallicity independent from the spectrum of light that it emits.« less

  13. [Internship-test reveals increased knowledge gaps].

    PubMed

    Östgren, Carl-Johan; Krook-Brandt, Margareta; Carlborg, Andreas

    2016-04-08

    We present the results of the medical knowledge test after fulfilled internship for Swedish medical authorization during the years 2009 to the spring of 2015. A total of 7,613 tests were analyzed. Interns graduated from Swedish universities failed in 2.7% to 3.8% of the test moments. Interns who graduated from countries within the European Union (EU) failed in 21.2% and interns graduated from a non-EU country failed in 41.6%. The results from those who graduated from EU and non-EU countries have worsened compared to an earlier study in 2009. Proper measures have now to be implemented for doctors graduated from a non-Swedish university to improve the outcome and introduction to the Swedish health care system.

  14. Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Pratt & Whitney Advanced Ducted Propulsor (ADP) Engine Test in 40x80ft w.t.: Engineers Peter Zell (left) and Dr Clifton Horne (right) are shown preparing for a laser light sheet for a flow visualization test. Shown standing in the nacelle of the ADP is John Girvin, senior test engineer for Pratt & Whitney.

  15. Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

    PubMed

    Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

    2017-11-21

    It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high

  16. Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer.

    PubMed

    Jiménez-Fonseca, Paula; Carmona-Bayonas, Alberto; Sánchez Lorenzo, Maria Luisa; Plazas, Javier Gallego; Custodio, Ana; Hernández, Raquel; Garrido, Marcelo; García, Teresa; Echavarría, Isabel; Cano, Juana María; Rodríguez Palomo, Alberto; Mangas, Monserrat; Macías Declara, Ismael; Ramchandani, Avinash; Visa, Laura; Viudez, Antonio; Buxó, Elvira; Díaz-Serrano, Asunción; López, Carlos; Azkarate, Aitor; Longo, Federico; Castañón, Eduardo; Sánchez Bayona, Rodrigo; Pimentel, Paola; Limón, Maria Luisa; Cerdá, Paula; Álvarez Llosa, Renata; Serrano, Raquel; Lobera, Maria Pilar Felices; Alsina, María; Hurtado Nuño, Alicia; Gómez-Martin, Carlos

    2017-05-01

    Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

  17. Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.

    PubMed

    Seys, Sven F; Scheers, Hans; Van den Brande, Paul; Marijsse, Gudrun; Dilissen, Ellen; Van Den Bergh, Annelies; Goeminne, Pieter C; Hellings, Peter W; Ceuppens, Jan L; Dupont, Lieven J; Bullens, Dominique M A

    2017-02-23

    Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking. Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10 th /90 th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles. Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13. We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

  18. Natural history of chronic hepatitis B: what exactly has REVEAL revealed?

    PubMed

    Iloeje, Uchenna H; Yang, Hwai-I; Chen, Chien-Jen

    2012-10-01

    Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL-HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver-related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver-related mortality compared with HBsAg -seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non-invasive clinical parameters to predict long-term HCC risk. These will hopefully contribute to evidence-based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL-HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL-HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward. © 2012 John Wiley & Sons A/S.

  19. The Screening Test for Emotional Problems--Teacher-Report Version (Step-T): Studies of Reliability and Validity

    ERIC Educational Resources Information Center

    Erford, Bradley T.; Butler, Caitlin; Peacock, Elizabeth

    2015-01-01

    The Screening Test for Emotional Problems-Teacher Version (STEP-T) was designed to identify students aged 7-17 years with wide-ranging emotional disturbances. Coefficients alpha and test-retest reliability were adequate for all subscales except Anxiety. The hypothesized five-factor model fit the data very well and external aspects of validity were…

  20. Flight Test of the Aerojet 7KS-6000 T-27 Jato Rocket Motor

    NASA Technical Reports Server (NTRS)

    Bond, Aleck C.; Thibodaux, Joseph G., Jr.

    1949-01-01

    A flight test of the Aero jet Engineering Corporation's 7KS-6000 T-27 Jato rocket motor was conducted at the Langley Pilotless Aircraft Research Station at Wallops Island, Va, to determine the flight performance characteristics of the motor. The flight test imposed an absolute longitudinal acceleration of 9.8 g upon the rocket motor at 2.8 seconds after launching. The total impulse developed by the motor was 43,400 pound-seconds, and the thrusting time was 7.58 seconds. The maximum thrust was 7200 pounds and occurred at 4.8 seconds after launching. No thrust irregularities attributable to effects of the flight longitudinal acceleration were observed. Certain small thrust irregularities occurred in the flight test which appear to correspond to irregularities observed in static tests conducted elsewhere. A hypothesis regarding the origin of these small irregularities is presented.

  1. A HUPO test sample study reveals common problems in mass spectrometry-based proteomics

    PubMed Central

    Bell, Alexander W.; Deutsch, Eric W.; Au, Catherine E.; Kearney, Robert E.; Beavis, Ron; Sechi, Salvatore; Nilsson, Tommy; Bergeron, John J.M.

    2009-01-01

    We carried out a test sample study to try to identify errors leading to irreproducibility, including incompleteness of peptide sampling, in LC-MS-based proteomics. We distributed a test sample consisting of an equimolar mix of 20 highly purified recombinant human proteins, to 27 laboratories for identification. Each protein contained one or more unique tryptic peptides of 1250 Da to also test for ion selection and sampling in the mass spectrometer. Of the 27 labs, initially only 7 labs reported all 20 proteins correctly, and only 1 lab reported all the tryptic peptides of 1250 Da. Nevertheless, a subsequent centralized analysis of the raw data revealed that all 20 proteins and most of the 1250 Da peptides had in fact been detected by all 27 labs. The centralized analysis allowed us to determine sources of problems encountered in the study, which include missed identifications (false negatives), environmental contamination, database matching, and curation of protein identifications. Improved search engines and databases are likely to increase the fidelity of mass spectrometry-based proteomics. PMID:19448641

  2. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

    PubMed Central

    Milush, Jeffrey M.; Mir, Kiran D.; Sundaravaradan, Vasudha; Gordon, Shari N.; Engram, Jessica; Cano, Christopher A.; Reeves, Jacqueline D.; Anton, Elizabeth; O’Neill, Eduardo; Butler, Eboneé; Hancock, Kathy; Cole, Kelly S.; Brenchley, Jason M.; Else, James G.; Silvestri, Guido; Sodora, Donald L.

    2011-01-01

    SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4–CD8– T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell–like helper functions upon SIV-induced CD4+ T cell depletion in this species. PMID:21317533

  3. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells.

    PubMed

    Milush, Jeffrey M; Mir, Kiran D; Sundaravaradan, Vasudha; Gordon, Shari N; Engram, Jessica; Cano, Christopher A; Reeves, Jacqueline D; Anton, Elizabeth; O'Neill, Eduardo; Butler, Eboneé; Hancock, Kathy; Cole, Kelly S; Brenchley, Jason M; Else, James G; Silvestri, Guido; Sodora, Donald L

    2011-03-01

    SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4(+) T cells to SIV-negative animals resulted in rapid loss of CD4(+) T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4(+) T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4(+) T cell-like helper functions upon SIV-induced CD4(+) T cell depletion in this species.

  4. Immunoproteomic analysis of house dust mite antigens reveals distinct classes of dominant T cell antigens according to function and serological reactivity

    PubMed Central

    Westernberg, Luise; Pham, John; Lane, Jerome; Paul, Sinu; Greenbaum, Jason; Stranzl, Thomas; Lund, Gitte; Hoof, Ilka; Holm, Jens; Würtzen, Peter A; Meno, Kåre H.; Frazier, April; Schulten, Veronique; Andersen, Peter S.; Peters, Bjoern; Sette, Alessandro

    2016-01-01

    BACKGROUND House dust mite (HDM) allergens are a common cause of allergy and allergic asthma. A comprehensive analysis of proteins targeted by T cells, which are implicated in the development and regulation of allergic disease independent of their antibody reactivity, is still lacking. OBJECTIVE To comprehensively analyze the HDM-derived protein targets of T cell responses in HDM-allergic individuals, and investigate their correlation with IgE/IgG responses and protein function. METHODS Proteomic analysis (liquid chromatography tandem mass spectrometry) of HDM extracts identified 90 distinct protein clusters, corresponding to 29 known allergens and 61 novel proteins. Peripheral blood mononuclear cells (PBMC) from 20 HDM-allergic individuals were stimulated with HDM extracts and assayed with a set of ~2500 peptides derived from these 90 protein clusters and predicted to bind the most common HLA class II types. 2D immunoblots were made in parallel to elucidate IgE and IgG reactivity and putative function analyses were performed in silico according to gene ontology (GO) annotations. RESULTS Analysis of T cell reactivity revealed a large number of T cell epitopes. Overall response magnitude and frequency was comparable for known and novel proteins, with 15 antigens (nine of which were novel) dominating the total T cell response. Most of the known allergens that were dominant at the T cell level were also IgE-reactive, as expected, while few novel dominant T cell antigens were IgE reactive. Among known allergens, hydrolase activity and detectable IgE/IgG reactivity are strongly correlated, while no protein function correlates with immunogenicity of novel proteins. A total of 106 epitopes accounted for half of the total T-cell response, underlining the heterogeneity of T cell responses to HDM allergens. CONCLUSIONS AND CLINICAL RELEVANCE Herein, we define the T cell targets for both known allergens and novel proteins, which may inform future diagnostics and

  5. Analysis of pumping tests: Significance of well diameter, partial penetration, and noise

    USGS Publications Warehouse

    Heidari, M.; Ghiassi, K.; Mehnert, E.

    1999-01-01

    The nonlinear least squares (NLS) method was applied to pumping and recovery aquifer test data in confined and unconfined aquifers with finite diameter and partially penetrating pumping wells, and with partially penetrating piezometers or observation wells. It was demonstrated that noiseless and moderately noisy drawdown data from observation points located less than two saturated thicknesses of the aquifer from the pumping well produced an exact or acceptable set of parameters when the diameter of the pumping well was included in the analysis. The accuracy of the estimated parameters, particularly that of specific storage, decreased with increases in the noise level in the observed drawdown data. With consideration of the well radii, the noiseless drawdown data from the pumping well in an unconfined aquifer produced good estimates of horizontal and vertical hydraulic conductivities and specific yield, but the estimated specific storage was unacceptable. When noisy data from the pumping well were used, an acceptable set of parameters was not obtained. Further experiments with noisy drawdown data in an unconfined aquifer revealed that when the well diameter was included in the analysis, hydraulic conductivity, specific yield and vertical hydraulic conductivity may be estimated rather effectively from piezometers located over a range of distances from the pumping well. Estimation of specific storage became less reliable for piezemeters located at distances greater than the initial saturated thickness of the aquifer. Application of the NLS to field pumping and recovery data from a confined aquifer showed that the estimated parameters from the two tests were in good agreement only when the well diameter was included in the analysis. Without consideration of well radii, the estimated values of hydraulic conductivity from the pumping and recovery tests were off by a factor of four.The nonlinear least squares method was applied to pumping and recovery aquifer test data in

  6. Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans.

    PubMed

    Cruz, E; Vieira, J; Gonçalves, R; Alves, H; Almeida, S; Rodrigues, P; Lacerda, R; Porto, G

    2004-07-01

    Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.

  7. Multimodal biopanning of T7 phage-displayed peptides reveals angiomotin as a potential receptor of the anti-angiogenic macrolide Roxithromycin.

    PubMed

    Takakusagi, Kaori; Takakusagi, Yoichi; Suzuki, Takahiro; Toizaki, Aya; Suzuki, Aiko; Kawakatsu, Yaichi; Watanabe, Madoka; Saito, Yukihiro; Fukuda, Ryushi; Nakazaki, Atsuo; Kobayashi, Susumu; Sakaguchi, Kengo; Sugawara, Fumio

    2015-01-27

    Roxithromycin (RXM) is a semi-synthetic fourteen-membered macrolide antibiotic that shows anti-angiogenic activity in solid tumors. In the present study, we conducted biopanning of T7 phage-displayed peptides either on a 96-well formatted microplate, a flow injection-type quartz-crystal microbalance (QCM) biosensor, or a cuvette-type QCM. RXM-selected peptides of different sequence, length and number were obtained from each mode of screening. Subsequent bioinformatics analysis of the RXM-selected peptides consistently gave positive scores for the extracellular domain (E458-T596) of angiomotin (Amot), indicating that this may comprise a binding region for RXM. Bead pull down assay and QCM analysis confirmed that RXM directly interacts with Amot via the screen-guided region, which also corresponds to the binding site for the endogenous anti-angiogenic inhibitor angiostatin (Anst). Thus, multimodal biopanning of T7PD revealed that RXM binds to the extracellular domain on Amot as a common binding site with Anst, leading to inhibition of angiogenesis-dependent tumor growth and metastasis. These data might explain the molecular basis underlying the mechanism of action for the anti-angiogenic activity of RXM. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Propulsion Control and Health Management (PCHM) Technology for Flight Test on the C-17 T-1 Aircraft

    NASA Technical Reports Server (NTRS)

    Simon, Donald L.; Garg, Sanjay; Venti, Michael

    2004-01-01

    The C-I 7 T-l Globemaster III is an Air Force flight research vehicle located at Edwards Air Force Base. NASA Dryden and the C-17 System Program Office have entered into a Memorandum of Agreement to permit NASA the use of the C-I 7 T-I to conduct flight research on a mutually coordinated schedule. The C-17 Propulsion Control and Health Management (PCHM) Working Group was formed in order to foster discussion and coordinate planning amongst the various government agencies conducting PCHM research with a potential need for flight testing, and to communicate to the PCHM community the capabilities of the C-17 T-l aircraft to support such flight testing. This paper documents the output of this Working Group, including a summary of the candidate PCHM technologies identified and their associated benefits relative to NASA goals and objectives.

  9. Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model.

    PubMed

    Sakkaki, Sophie; Gangarossa, Giuseppe; Lerat, Benoit; Françon, Dominique; Forichon, Luc; Chemin, Jean; Valjent, Emmanuel; Lerner-Natoli, Mireille; Lory, Philippe

    2016-02-01

    T-type (Cav3) calcium channels play important roles in neuronal excitability, both in normal and pathological activities of the brain. In particular, they contribute to hyper-excitability disorders such as epilepsy. Here we have characterized the anticonvulsant properties of TTA-A2, a selective T-type channel blocker, in mouse. Using the maximal electroshock seizure (MES) as a model of tonic-clonic generalized seizures, we report that mice treated with TTA-A2 (0.3 mg/kg and higher doses) were significantly protected against tonic seizures. Although no major change in Local Field Potential (LFP) pattern was observed during the MES seizure, analysis of the late post-ictal period revealed a significant increase in the delta frequency power in animals treated with TTA-A2. Similar results were obtained for Cav3.1-/- mice, which were less prone to develop tonic seizures in the MES test, but not for Cav3.2-/- mice. Analysis of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and c-Fos expression revealed a rapid and elevated neuronal activation in the hippocampus following MES clonic seizures, which was unchanged in TTA-A2 treated animals. Overall, our data indicate that TTA-A2 is a potent anticonvulsant and that the Cav3.1 isoform plays a prominent role in mediating TTA-A2 tonic seizure protection. Copyright © 2015. Published by Elsevier Ltd.

  10. Physical and genetic-interaction density reveals functional organization and informs significance cutoffs in genome-wide screens

    PubMed Central

    Dittmar, John C.; Pierce, Steven; Rothstein, Rodney; Reid, Robert J. D.

    2013-01-01

    Genome-wide experiments often measure quantitative differences between treated and untreated cells to identify affected strains. For these studies, statistical models are typically used to determine significance cutoffs. We developed a method termed “CLIK” (Cutoff Linked to Interaction Knowledge) that overlays biological knowledge from the interactome on screen results to derive a cutoff. The method takes advantage of the fact that groups of functionally related interacting genes often respond similarly to experimental conditions and, thus, cluster in a ranked list of screen results. We applied CLIK analysis to five screens of the yeast gene disruption library and found that it defined a significance cutoff that differed from traditional statistics. Importantly, verification experiments revealed that the CLIK cutoff correlated with the position in the rank order where the rate of true positives drops off significantly. In addition, the gene sets defined by CLIK analysis often provide further biological perspectives. For example, applying CLIK analysis retrospectively to a screen for cisplatin sensitivity allowed us to identify the importance of the Hrq1 helicase in DNA crosslink repair. Furthermore, we demonstrate the utility of CLIK to determine optimal treatment conditions by analyzing genome-wide screens at multiple rapamycin concentrations. We show that CLIK is an extremely useful tool for evaluating screen quality, determining screen cutoffs, and comparing results between screens. Furthermore, because CLIK uses previously annotated interaction data to determine biologically informed cutoffs, it provides additional insights into screen results, which supplement traditional statistical approaches. PMID:23589890

  11. Increased anti-tumor effects using IL2 with anti-TGFβ reveals competition between mouse NK and CD8 T cells

    PubMed Central

    Alvarez, Maite; Bouchlaka, Myriam N.; Sckisel, Gail D.; Sungur, Can M.; Chen, Mingyi; Murphy, William J.

    2014-01-01

    Due to increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL2 with antibodies to neutralize TGFβ, a potent immunosuppressive cytokine, was assessed. Combination immunotherapy resulted in significantly greater anti-tumor effects. These were correlated with significant increases in the numbers and functionality of NK cells, NK progenitors and activated CD8 T cells resulting in the observed anti-tumor effects. Combination immunotherapy was also accompanied with lesser toxicities than IL2 therapy alone. Additionally, we observed a dual competition between NK and activated CD8 T cells such that after immunotherapy, the depletion of either effector population resulted in the increased total expansion of the other population and compensatory anti-tumor effects. This study demonstrates the efficacy of this combination immunotherapeutic regimen as a promising cancer therapy and illustrates the existence of potent competitive regulatory pathways between NK and CD8 T cells in response to systemic activation. PMID:25000978

  12. Dynamic Interaction- and Phospho-Proteomics Reveal Lck as a Major Signaling Hub of CD147 in T Cells.

    PubMed

    Supper, Verena; Hartl, Ingrid; Boulègue, Cyril; Ohradanova-Repic, Anna; Stockinger, Hannes

    2017-03-15

    Numerous publications have addressed CD147 as a tumor marker and regulator of cytoskeleton, cell growth, stress response, or immune cell function; however, the molecular functionality of CD147 remains incompletely understood. Using affinity purification, mass spectrometry, and phosphopeptide enrichment of isotope-labeled peptides, we examined the dynamic of the CD147 microenvironment and the CD147-dependent phosphoproteome in the Jurkat T cell line upon treatment with T cell stimulating agents. We identified novel dynamic interaction partners of CD147 such as CD45, CD47, GNAI2, Lck, RAP1B, and VAT1 and, furthermore, found 76 CD147-dependent phosphorylation sites on 57 proteins. Using the STRING protein network database, a network between the CD147 microenvironment and the CD147-dependent phosphoproteins was generated and led to the identification of key signaling hubs around the G proteins RAP1B and GNB1, the kinases PKCβ, PAK2, Lck, and CDK1, and the chaperone HSPA5. Gene ontology biological process term analysis revealed that wound healing-, cytoskeleton-, immune system-, stress response-, phosphorylation- and protein modification-, defense response to virus-, and TNF production-associated terms are enriched within the microenvironment and the phosphoproteins of CD147. With the generated signaling network and gene ontology biological process term grouping, we identify potential signaling routes of CD147 affecting T cell growth and function. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. Significance of "stretched" mineral inclusions for reconstructing P- T exhumation history

    NASA Astrophysics Data System (ADS)

    Ashley, Kyle T.; Darling, Robert S.; Bodnar, Robert J.; Law, Richard D.

    2015-06-01

    Analysis of mineral inclusions in chemically and physically resistant hosts has proven to be valuable for reconstructing the P- T exhumation history of high-grade metamorphic rocks. The occurrence of cristobalite-bearing inclusions in garnets from Gore Mountain, New York, is unexpected because the peak metamorphic conditions reached are well removed (>600 °C too cold) from the stability field of this low-density silica polymorph that typically forms in high temperature volcanic environments. A previous study of samples from this area interpreted polymineralic inclusions consisting of cristobalite, albite and ilmenite as representing crystallized droplets of melt generated during a garnet-in reaction, followed by water loss from the inclusion to explain the reduction in inclusion pressure that drove the transformation of quartz to cristobalite. However, the recent discovery of monomineralic inclusions of cristobalite from the nearby Hooper Mine cannot be explained by this process. For these inclusions, we propose that the volume response to pressure and temperature changes during exhumation to Earth's surface resulted in large tensile stresses within the silica phase that would be sufficient to cause transformation to the low-density (low-pressure) form. Elastic modeling of other common inclusion-host systems suggests that this quartz-to-cristobalite example may not be a unique case. The aluminosilicate polymorph kyanite also has the capacity to retain tensile stresses if exhumed to Earth's surface after being trapped as an inclusion in plagioclase at P- T conditions within the kyanite stability field, with the stresses developed during exhumation sufficient to produce a transformation to andalusite. These results highlight the elastic environment that may arise during exhumation and provide a potential explanation of observed inclusions whose stability fields are well removed from P- T paths followed during exhumation.

  14. Revealing physical education students’ misconception in sport biomechanics

    NASA Astrophysics Data System (ADS)

    Kartiko, D. C.

    2018-04-01

    The aim of this research is reveal Physical Education students’ misconception in several concepts of Sport Biomechanics. The Data of misconception collected by standard question of Diagnostic Test that given to 30 students of Physical Education, Faculty of Sport, State University of Surabaya in academic year 2017/2018. Diagnostic Test completed with CRI (Certainty of Response Index) in order to collect data of students’ certain in answered test. The data result of diagnostic test analysed through compilation graph of CRI right, CRI wrong and right fraction in every single question. Furthermore, students’ answer result of diagnostic test categorized in to 4 quadrants, these: correct concepts, lucky guess, misconceptions, and lack of knowledge. Its categorizing data to know percentage of misconceptions that arise in every concept tested. These sport biomechanics concepts tested are limited on frictional force, deference of distance and displacement, deference of velocity and acceleration, and free fall motion. The result obtained arise misconception in frictional force 52,78%; deference of distance and displacement 36,67%; deference of velocity and acceleration 56,67%; and free fall motion 53,33%. Result of t-test in diagnostic test misconception percentage showed that percentage of misconception arises in every student above 50%.

  15. Comprehensive evaluation of the estrogen receptor alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population.

    PubMed

    Keene, Keith L; Mychaleckyj, Josyf C; Smith, Shelly G; Leak, Tennille S; Perlegas, Peter S; Langefeld, Carl D; Herrington, David M; Freedman, Barry I; Rich, Stephen S; Bowden, Donald W; Sale, Michèle M

    2008-05-01

    We previously investigated the estrogen receptor alpha gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and T2DM and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and end stage renal disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a chi(2) statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P < 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P = 0.000291, adjusted P = 0.0289), and intron 4 SNPs rs1569788 (nominal P = 0.000754, adjusted P = 0.0278) and rs9340969 (nominal P = 0.00109, adjusted P = 0.0467) remained significant at experimentwise error rate (EER) P tests. Twenty-three of the thirty-one associated SNPs cluster within the intron 4-intron 6 regions. Gender stratification revealed nominal evidence for association with 35 SNPs in females (352 cases; 306 controls) and seven SNPs in males (225 cases; 290 controls). We have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy.

  16. PCR reveals significantly higher rates of Trypanosoma cruzi infection than microscopy in the Chagas vector, Triatoma infestans: High rates found in Chuquisaca, Bolivia

    PubMed Central

    Pizarro, Juan Carlos; Lucero, David E; Stevens, Lori

    2007-01-01

    AGC GGA TAG TTC AGG – 3') primers. Amplicons were chromatographed on a 2% agarose gel with a 100 bp size standard, stained with ethidium bromide and viewed with UV fluorescence. For both the microscopy and PCR assays, we calculated sensitivity (number of positives by a method divided by the number of positives by either method) and discrepancy (one method was negative and the other was positive) at the locality, life stage and habitat level. The degree of agreement between PCR and microscopy was determined by calculating Kappa (k) values with 95% confidence intervals. Results We observed a high prevalence of T. cruzi infection in T. infestans (81.16% by PCR and 56.52% by microscopy) and discovered that PCR is significantly more sensitive than microscopic observation. The overall degree of agreement between the two methods was moderate (Kappa = 0.43 ± 0.07). The level of infection is significantly different among communities; however, prevalence was similar among habitats and life stages. Conclusion PCR was significantly more sensitive than microscopy in all habitats, developmental stages and localities in Chuquisaca, Bolivia. Overall we observed a high prevalence of T. cruzi infection in T. infestans in this area of Bolivia; however, microscopy underestimated infection at all levels examined. PMID:17597541

  17. Blister Test for Measurements of Adhesion and Adhesion Degradation of Organic Polymers on AA2024-T3

    NASA Astrophysics Data System (ADS)

    Rincon Troconis, Brendy Carolina

    A key parameter for the performance of corrosion protective coatings applied to metals is adhesion. Surface preparation prior to coating application is known to be critical, but there is a lack of understanding of what controls adhesion. Numerous techniques have been developed in the last decades to measure the adhesion strength of coatings to metals. Nonetheless, they are generally non-quantitative, non-reproducible, performed in dry conditions, or overestimate adhesion. In this study, a quantitative and reproducible technique, the Blister Test (BT), is used. The BT offers the ability to study the effects of a range of parameters, including the presence or absence of a wetting liquid, and simulates the stress situation in the coating/substrate interface. The effects of roughness and surface topography were studied by the BT and Optical Profilometry, using AA2024-T3 substrates coated with polyvinyl butyral (PVB). Random abrasion generated a surface with lower average roughness than aligned abrasion due to the continual cross abrasion of the grooves. The BT could discern the effects of different mechanical treatments. An adhesion strength indicator was defined and found to be a useful parameter. The effectiveness of standard adhesion techniques such as ASTM D4541 (Pull-off Test) and ASTM D3359 (Tape Test) was compared to the BT. Also, different attempts to measure adhesion and adhesion degradation of organic polymers to AA2024-T3 were tested. The pull-off test does not produce adhesive failure across the entire interface, while the tape test is a very qualitative technique and does not discern between the effects of different coating systems on the adhesion performance. The BT produces adhesive failure of the primer studied, is very reproducible, and is able to rank different coating systems. Therefore, it was found to be superior to the others. The approaches tested for adhesion degradation were not aggressive enough to have a measurable effect. The effects of

  18. Evaluating significance in linear mixed-effects models in R.

    PubMed

    Luke, Steven G

    2017-08-01

    Mixed-effects models are being used ever more frequently in the analysis of experimental data. However, in the lme4 package in R the standards for evaluating significance of fixed effects in these models (i.e., obtaining p-values) are somewhat vague. There are good reasons for this, but as researchers who are using these models are required in many cases to report p-values, some method for evaluating the significance of the model output is needed. This paper reports the results of simulations showing that the two most common methods for evaluating significance, using likelihood ratio tests and applying the z distribution to the Wald t values from the model output (t-as-z), are somewhat anti-conservative, especially for smaller sample sizes. Other methods for evaluating significance, including parametric bootstrapping and the Kenward-Roger and Satterthwaite approximations for degrees of freedom, were also evaluated. The results of these simulations suggest that Type 1 error rates are closest to .05 when models are fitted using REML and p-values are derived using the Kenward-Roger or Satterthwaite approximations, as these approximations both produced acceptable Type 1 error rates even for smaller samples.

  19. Test and Evaluation (T&E)

    DTIC Science & Technology

    2013-03-04

    AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Air Force Office of...Scientific Research ,AFOSR/RTA,875 N. Randolph,Arlington,VA,22203 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND...transitioning revolutionary science to DoD and industry 7 Distribution A: Approved for public release; distribution is unlimited Air Force T&E Organization

  20. Wada testing reveals frontal lateralization for the memorization of words and faces.

    PubMed

    Kelley, W M; Ojemann, J G; Wetzel, R D; Derdeyn, C P; Moran, C J; Cross, D T; Dowling, J L; Miller, J W; Petersen, S E

    2002-01-01

    Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.

  1. Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity.

    PubMed

    Nagafuchi, Yasuo; Shoda, Hirofumi; Sumitomo, Shuji; Nakachi, Shinichiro; Kato, Rika; Tsuchida, Yumi; Tsuchiya, Haruka; Sakurai, Keiichi; Hanata, Norio; Tateishi, Shoko; Kanda, Hiroko; Ishigaki, Kazuyoshi; Okada, Yukinori; Suzuki, Akari; Kochi, Yuta; Fujio, Keishi; Yamamoto, Kazuhiko

    2016-07-07

    Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4(+)CD4(+) T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4(+)CD4(+) T cells. Moreover, the frequency of memory CXCR4(+)CD4(+) T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4(+)CD4(+) T cells. Clinically, a higher frequency of memory CXCR4(+)CD4(+) T cells predicted a better response to CTLA4-Ig. Memory CXCR4(+)CD4(+) T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA.

  2. Activation of the DLPFC Reveals an Asymmetric Effect in Risky Decision Making: Evidence from a tDCS Study

    PubMed Central

    Huang, Daqiang; Chen, Shu; Wang, Siqi; Shi, Jinchuan; Ye, Hang; Luo, Jun; Zheng, Haoli

    2017-01-01

    The phenomenon of loss aversion (the tendency for losses to have a greater impact than comparable gains) has long been observed in daily life. Neurocognitive studies and brain imaging studies have shed light on the correlation between the phenomenon of loss aversion and the brain region of the prefrontal cortex. Recent brain stimulation studies using bilateral transcranial magnetic stimulation or transcranial direct current stimulation (tDCS) have obtained various results showing the causal relationship between brain regions and decision making. With the goal of studying whether unilateral stimulation can change participants’ risky decision making in the frames of gains and losses, we applied different polarities of tDCS over the regions of the right or left prefrontal cortex. We also designed a risk measurement table (Multiple Price List) to reflect the participants’ attitudes toward risky decision making via the crossover point including the frames of gains and losses. The results of our experiment indicated that the participants tended to be more risk averse in the gain frame after receiving left anodal tDCS and more risk seeking in the loss frame after receiving right cathodal tDCS, which was consistent with the hypothesis that the process of risky decision making was correlated with the interaction of multiple systems in the brain. Our conclusion revealed an asymmetric effect of right/left DLPFC when the participants faced gains and losses, which partially provided the neural evidence and a feasible paradigm to help better understand risky decision making and loss aversion. The current study can not only expand the traditional understanding of the behavioral preferences of humans in economics but also accommodate empirical observations of behavioral economists on the preferences of humans. PMID:28174549

  3. PEP Integrated Test D Run Report Caustic and Oxidative Leaching in UFP-VSL-T02A

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sevigny, Gary J.; Bredt, Ofelia P.; Burns, Carolyn A.

    2009-12-11

    Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes" of the External Flowsheet Review Team (EFRT) issue response plan. The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes. Themore » PEP replicates the WTP leaching processes using prototypic equipment and control strategies. The PEP also includes non-prototypic ancillary equipment to support the core processing. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario (Test B and D) has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario (Test A) has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP and vessels UFP VSL-00001A and B in the WTP PTF). In Test D, 19M sodium hydroxide (NaOH, caustic) was added to the waste slurry in the UFP VSL T02 vessel after the solids were concentrated to ~20% undissolved solids. The NaOH was added to leach solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by heating to 85°C using direct injection of steam to accelerate the leach process. The main difference of Test D compared to Test B is that the leach temperature is 85°C for 24 hrs as compared to 100°C for 12 hours. The other difference is the Test D simulant had Cr in

  4. Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance

    PubMed Central

    Spada, E; Mele, A; Berton, A; Ruggeri, L; Ferrigno, L; Garbuglia, A R; Perrone, M P; Girelli, G; Del Porto, P; Piccolella, E; Mondelli, M U; Amoroso, P; Cortese, R; Nicosia, A; Vitelli, A; Folgori, A

    2004-01-01

    Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. Conclusion: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment. PMID:15479691

  5. Comparison of cost-effectiveness between the quantiFERON-TB Gold-In-Tube and T-Spot tests for screening health-care workers for latent tuberculosis infection.

    PubMed

    Mukai, Shigeto; Shigemura, Katsumi; Yamamichi, Fukashi; Kitagawa, Koichi; Takami, Nozomi; Nomi, Masashi; Arakawa, Soichi; Fujisawa, Masato

    2017-01-01

    There are several methods used to screen for latent tuberculosis (TB) infection (LTBI) including the QuantiFERON-TB Gold-in-Tube (QFT-GIT) and T-SPOT-TB (T-SPOT) tests. Many studies have reported the equivalence of these two methods, but it is unclear which of them is more cost effective. We investigated the age and cost issues of these tests in screening for LTBI among health-care workers. One hundred and forty new employees during 2008-2011 in our hospital were screened using the QFT-GIT test, and 140 new employees during 2011-2014 were screened with the T-SPOT test for LTBI. The results of both tests were classified as positive, undetermined (retesting required), or negative. There were six positive results (4.29%), eight undetermined results (5.71%), and 126 negative results (90.0%) with the QFT-GIT test. As for the T-SPOT test, there were eight positive results (5.71%), three undetermined results (2.14%), and 129 negative results (92.1%). Fourteen LTBI employees (6 in QFT-GIT and 8 in T-SPOT) were detected statistically equally using the two methods (P = 0.79). The total costs, including those incurred for retesting, were $7,711.86 (US dollar) and $6,525.42 for the QFT-GIT and T-SPOT tests (cost of one test is $55.08 for QFT-GIT and $46.61 for T-SPOT), respectively. T-SPOT is one of the options for screening for LTBI partly owing to the viewpoint of cost-effectiveness. Further prospective studies need to be considered for a definitive conclusion.

  6. Raman spectrum reveals the cell cycle arrest of Triptolide-induced leukemic T-lymphocytes apoptosis

    NASA Astrophysics Data System (ADS)

    Zhang, Daosen; Feng, Yanyan; Zhang, Qinnan; Su, Xin; Lu, Xiaoxu; Liu, Shengde; Zhong, Liyun

    2015-04-01

    Triptolide (TPL), a traditional Chinese medicine extract, possesses anti-inflammatory and anti-tumor properties. Though some research results have implicated that Triptolide (TPL) can be utilized in the treatment of leukemia, it remains controversial about the mechanism of TPL-induced leukemic T-lymphocytes apoptosis. In this study, combining Raman spectroscopic data, principal component analysis (PCA) and atomic force microscopy (AFM) imaging, both the biochemical changes and morphological changes during TPL-induced cell apoptosis were presented. In contrast, the corresponding data during Daunorubicin (DNR)-induced cell apoptosis was also exhibited. The obtained results showed that Raman spectral changes during TPL-induced cell apoptosis were greatly different from DNR-induced cell apoptosis in the early stage of apoptosis but revealed the high similarity in the late stage of apoptosis. Moreover, above Raman spectral changes were respectively consistent with the morphological changes of different stages during TPL-induced apoptosis or DNR-induced apoptosis, including membrane shrinkage and blebbing, chromatin condensation and the formation of apoptotic bodies. Importantly, it was found that Raman spectral changes with TPL-induced apoptosis or DNR-induced apoptosis were respectively related with the cell cycle G1 phase arrest or G1 and S phase arrest.

  7. ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis.

    PubMed

    Al-Rubeaan, Khalid; Siddiqui, Khalid; Saeb, Amr T M; Nazir, Nyla; Al-Naqeb, Dhekra; Al-Qasim, Sara

    2013-05-15

    In this meta-analysis study, SNPs were investigated for their association with type 2 diabetes (T2D) in both Arab and Caucasian ethnicities. A total of 55 SNPs were analyzed, of which 11 fulfilled the selection criteria, and were used for analysis. It was found that TCF7L2 rs7903146 was significantly associated with a pooled OR of 1.155 (95%C.I.=1.059-1.259), p<0.0001 and I(2)=78.30% among the Arab population, whereas among Caucasians, the pooled OR was 1.45 (95%C.I.=1.386-1.516), p<0.0001 and I(2)=77.20%. KCNJ11 rs5219 was significantly associated in both the populations with a pooled OR of 1.176(1.092-1.268), p<0.0001 and I(2)=32.40% in Caucasians and a pooled OR of 1.28(1.111-1.475), p=0.001 among Arabs. The ACE I/D polymorphism was found to be significantly associated with a pooled OR of 1.992 (95%C.I.=1.774-2.236), p<0.0001 and I(2)=83.20% among the Arab population, whereas among Caucasians, the pooled OR was 1.078 (95%C.I.=0.993-1.17), p=0.073 and I(2)=0%. Similarly, MTHFR C677T polymorphism was also found to be significantly associated among Arabs with a pooled OR of 1.924 (95%C.I.=1.606-2.304), p<0.0001 and I(2)=27.20%, whereas among Caucasians, the pooled OR was 0.986 (95%C.I.=0.868-1.122), p=0.835 and I(2)=0%. Meanwhile PPARG-2 Pro12Ala, CDKN2A/2B rs10811661, IGF2BP2 rs4402960, HHEX rs7923837, CDKAL1 rs7754840, EXT2 rs1113132 and SLC30A8 rs13266634 were found to have no significant association with T2D among Arabs. In conclusion, it seems from this study that both Arabs and Caucasians have different SNPs associated with T2D. Moreover, this study sheds light on the profound necessity for further investigations addressing the question of the genetic components of T2D in Arabs. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Axial Fatigue Tests at Zero Mean Stress of 24S-T and 75S-T Aluminum-alloy Strips with a Central Circular Hole

    NASA Technical Reports Server (NTRS)

    Brueggeman, W C; Mayer, M JR

    1948-01-01

    Axial fatigue tests at zero mean stress have been made on 0.032- and 0.064-inch 24S-T and 0.032-inch 75S-T sheet-metal specimens 1/4, 1/2, 1, and 2 inches wide without a hole and with central holes giving a range of hole diameter D to specimen width W from 0.01 to 0.95. No systematic difference was noted between the results for the 0.032-inch and the 0.064-inch specimens although the latter seemed the more consistent. In general the fatigue strength based on the minimum section dropped sharply as the ration D/W was increased from zero to about 0.25. The plain specimens showed quite a pronounced decrease in fatigue strength with increasing width. The holed specimens showed only slight and rather inconclusive evidence of this size effect. The fatigue stress-concentration factor was higher for 75S-T than for 24S-T alloy. Evidence was found that a very small hole would not cause any reduction in fatigue strength.

  9. The Trypanosoma cruzi Satellite DNA OligoC-TesT and Trypanosoma cruzi Kinetoplast DNA OligoC-TesT for Diagnosis of Chagas Disease: A Multi-cohort Comparative Evaluation Study

    PubMed Central

    De Winne, Koen; Büscher, Philippe; Luquetti, Alejandro O.; Tavares, Suelene B. N.; Oliveira, Rodrigo A.; Solari, Aldo; Zulantay, Ines; Apt, Werner; Diosque, Patricio; Monje Rumi, Mercedes; Gironès, Nuria; Fresno, Manuel; Lopez-Velez, Rogelio; Perez-Molina, José A.; Monge-Maillo, Begoña; Garcia, Lineth; Deborggraeve, Stijn

    2014-01-01

    Background The Trypanosoma cruzi satellite DNA (satDNA) OligoC-TesT is a standardised PCR format for diagnosis of Chagas disease. The sensitivity of the test is lower for discrete typing unit (DTU) TcI than for TcII-VI and the test has not been evaluated in chronic Chagas disease patients. Methodology/Principal Findings We developed a new prototype of the OligoC-TesT based on kinetoplast DNA (kDNA) detection. We evaluated the satDNA and kDNA OligoC-TesTs in a multi-cohort study with 187 chronic Chagas patients and 88 healthy endemic controls recruited in Argentina, Chile and Spain and 26 diseased non-endemic controls from D.R. Congo and Sudan. All specimens were tested in duplicate. The overall specificity in the controls was 99.1% (95% CI 95.2%–99.8%) for the satDNA OligoC-TesT and 97.4% (95% CI 92.6%–99.1%) for the kDNA OligoC-TesT. The overall sensitivity in the patients was 67.9% (95% CI 60.9%–74.2%) for the satDNA OligoC-TesT and 79.1% (95% CI 72.8%–84.4%) for the kDNA OligoC-Test. Conclusions/Significance Specificities of the two T. cruzi OligoC-TesT prototypes are high on non-endemic and endemic controls. Sensitivities are moderate but significantly (p = 0.0004) higher for the kDNA OligoC-TesT compared to the satDNA OligoC-TesT. PMID:24392177

  10. Association between GNB3 c.825C > T polymorphism and the risk of overweight and obesity: A meta-analysis.

    PubMed

    Li, Hui-Lan; Zhang, Yan-Jiao; Chen, Xiao-Ping; Luo, Jian-Quan; Liu, Si-Yun; Zhang, Zan-Lin

    2016-09-01

    The association between G protein β-polypeptide 3 gene (GNB3) c.825C > T polymorphism (rs5443) and the risk of overweight/obesity has been investigated in many published studies, but the results were conflicting and inconclusive. A meta-analysis was performed to make a more accurate assessment of the relationship. The PubMed, ProQuest Health & Medical Complete, Web of Science, Chinese Biomedical Medical databases (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched to identify eligible literatures. Pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were used to assess the strength of association between GNB3 c.825C > T polymorphism and overweight/obesity. Eleven articles including 15 case-control studies with a total of 10,396 subjects (3171 cases of overweight/obesity and 7225 controls) were enrolled in the meta-analysis. The GNB3 c.825C > T was significantly associated with overweight/obesity under a recessive model (OR = 1.22, 95% CI: 1.04-1.44, P = 0.015). Moreover, the GNB3 825T allele was obviously associated with overweight alone in all inheritable models (P < 0.05) except in a recessive model (P = 0.084). In the stratification analysis by potential confounding variables, a significant association was observed between GNB3 c.825C > T polymorphism and overweight/obesity risk in males under an allelic model (P = 0.008), a homozygous model (P = 0.014), a recessive model (P = 0.005), and a dominant model (P = 0.049). And the results also showed that GNB3 c.825C > T polymorphism was significantly associated with overweight/obesity in subgroups of mean age less than 30 years, consistent with HWE, and high-quality studies (P = 0.027, P = 0.043, P = 0.040, respectively) under a recessive model, but not in other subgroups. Meta-regression also revealed that P value of HWE, publication year, and the quality scores of studies were the sources of heterogeneity in a

  11. An anti-hapten camelid antibody reveals a cryptic binding site with significant energetic contributions from a nonhypervariable loop

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fanning, Sean W.; Horn, James R.

    2014-03-05

    Conventional anti-hapten antibodies typically bind low-molecular weight compounds (haptens) in the crevice between the variable heavy and light chains. Conversely, heavy chain-only camelid antibodies, which lack a light chain, must rely entirely on a single variable domain to recognize haptens. While several anti-hapten VHHs have been generated, little is known regarding the underlying structural and thermodynamic basis for hapten recognition. Here, an anti-methotrexate VHH (anti-MTX VHH) was generated using grafting methods whereby the three complementarity determining regions (CDRs) were inserted onto an existing VHH framework. Thermodynamic analysis of the anti-MTX VHH CDR1-3 Graft revealed a micromolar binding affinity, while themore » crystal structure of the complex revealed a somewhat surprising noncanonical binding site which involved MTX tunneling under the CDR1 loop. Due to the close proximity of MTX to CDR4, a nonhypervariable loop, the CDR4 loop sequence was subsequently introduced into the CDR1-3 graft, which resulted in a dramatic 1000-fold increase in the binding affinity. Crystal structure analysis of both the free and complex anti-MTX CDR1-4 graft revealed CDR4 plays a significant role in both intermolecular contacts and binding site conformation that appear to contribute toward high affinity binding. Additionally, the anti-MTX VHH possessed relatively high specificity for MTX over closely related compounds aminopterin and folate, demonstrating that VHH domains are capable of binding low-molecular weight ligands with high affinity and specificity, despite their reduced interface.« less

  12. Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.

    PubMed

    Kim, Young-Woo; Eom, Bang Wool; Kook, Myeong-Cherl; Kim, Han-Seong; Kim, Mi-Kyung; Hwang, Hai-Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae-Soo; Bae, Chang-Dae; Ro, Jungsil; Hong, Kyeong-Man

    2015-11-06

    Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.

  13. Trophic Mode-Dependent Proteomic Analysis Reveals Functional Significance of Light-Independent Chlorophyll Synthesis in Synechocystis sp. PCC 6803.

    PubMed

    Fang, Longfa; Ge, Haitao; Huang, Xiahe; Liu, Ye; Lu, Min; Wang, Jinlong; Chen, Weiyang; Xu, Wu; Wang, Yingchun

    2017-01-09

    The photosynthetic model organism Synechocystis sp. PCC 6803 can grow in different trophic modes, depending on the availability of light and exogenous organic carbon source. However, how the protein profile changes to facilitate the cells differentially propagate in different modes has not been comprehensively investigated. Using isobaric labeling-based quantitative proteomics, we simultaneously identified and quantified 45% Synechocystis proteome across four different trophic modes, i.e., autotrophic, heterotrophic, photoheterotrophic, and mixotrophic modes. Among the 155 proteins that are differentially expressed across four trophic modes, proteins involved in nitrogen assimilation and light-independent chlorophyll synthesis are dramatically upregulated in the mixotrophic mode, concomitant with a dramatic increase of P II phosphorylation that senses carbon and nitrogen assimilation status. Moreover, functional study using a mutant defective in light-independent chlorophyll synthesis revealed that this pathway is important for chlorophyll accumulation under a cycled light/dark illumination regime, a condition mimicking day/night cycles in certain natural habitats. Collectively, these results provide the most comprehensive information on trophic mode-dependent protein expression in cyanobacterium, and reveal the functional significance of light-independent chlorophyll synthesis in trophic growth. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  14. Clinical significance of the glucose breath test in patients with inflammatory bowel disease.

    PubMed

    Lee, Ji Min; Lee, Kang-Moon; Chung, Yoon Yung; Lee, Yang Woon; Kim, Dae Bum; Sung, Hea Jung; Chung, Woo Chul; Paik, Chang-Nyol

    2015-06-01

    Small intestinal bacterial overgrowth which has recently been diagnosed with the glucose breath test is characterized by excessive colonic bacteria in the small bowel, and results in gastrointestinal symptoms that mimic symptoms of inflammatory bowel disease. This study aimed to estimate the positivity of the glucose breath test and investigate its clinical role in inflammatory bowel disease. Patients aged > 18 years with inflammatory bowel disease were enrolled. All patients completed symptom questionnaires. Fecal calprotectin level was measured to evaluate the disease activity. Thirty historical healthy controls were used to determine normal glucose breath test values. A total of 107 patients, 64 with ulcerative colitis and 43 with Crohn's disease, were included. Twenty-two patients (20.6%) were positive for the glucose breath test (30.2%, Crohn's disease; 14.1%, ulcerative colitis). Positive rate of the glucose breath test was significantly higher in patients with Crohn's disease than in healthy controls (30.2% vs 6.7%, P=0.014). Bloating, flatus, and satiety were higher in glucose breath test-positive patients than glucose breath test-negative patients (P=0.021, 0.014, and 0.049, respectively). The positivity was not correlated with the fecal calprotectin level. The positive rate of the glucose breath test was higher in patients with inflammatory bowel disease, especially Crohn's disease than in healthy controls; gastrointestinal symptoms of patients with inflammatory bowel disease were correlated with this positivity. Glucose breath test can be used to manage intestinal symptoms of patients with inflammatory bowel disease. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  15. Evaluation of the need for routine clinical testing of PALB2 c.1592delT mutation in BRCA negative Northern Finnish breast cancer families.

    PubMed

    Haanpää, Maria; Pylkäs, Katri; Moilanen, Jukka S; Winqvist, Robert

    2013-08-13

    Testing for mutations in the BRCA1 and BRCA2 genes among high-risk breast cancer patients has become a routine practice among clinical geneticists. Unfortunately, however, the genetic background of a majority of the cases coming to the clinics remains currently unexplained, making genetic counseling rather challenging. In recent years it has become evident world-wide that also women carrying a heterozygous germline mutation in PALB2 are at significantly increased risk of getting breast cancer. We have previously studied the clinical as well as biological impact of the PALB2 c.1592delT founder mutation occurring in about 1% of Finnish breast cancer patients unselected for their family history of disease, and our results demonstrated a 40% increased breast cancer risk by age 70 for female mutation carriers. Thus, this relatively common mutation in PALB2 is associated with a high risk of developing breast cancer. The aim of the current study was to analyze whether female index individuals of breast cancer families who had tested negative for germline mutations in BRCA1/BRCA2 as part of genetic counseling services should be offered mutation testing for PALB2 c.1592delT. The study cohort consisted of altogether 223 individuals who had contacted the Department of Clinical Genetics at the Oulu University Hospital in Finland between the years 1997 and 2011 for counseling on hereditary breast and/or ovarian cancer risk. 101 of them met our inclusion criteria. Of these, 10 persons were now deceased, but 6 of them had participated in one of our previous studies on PALB2. Seventy (77%) of the remaining 91 persons responded positively to our study invitation. Chart review of updated pedigree data led to the exclusion of 14 further individuals not meeting the selection criteria. Of the 56 alive affected female individuals screened for PALB2 c.1592delT, altogether two (3.6%) tested positive for this mutation. In addition, of the previously tested but now deceased 6 persons

  16. Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers

    PubMed Central

    Mariano, Timothy Y.; Wout, Mascha van't; Garnaat, Sarah L.; Rasmussen, Steven A.; Greenberg, Benjamin D.

    2016-01-01

    Objective Current chronic pain treatments target nociception rather than affective “suffering” and its associated functional and psychiatric comorbidities. Left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can noninvasively modulate cortical activity. The present study tests if anodal tDCS targeting left DLPFC will increase tolerability of acute painful stimuli versus cathodal tDCS. Methods Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. Results Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (all p > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal versus cathodal tDCS (p = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (p = 0.042) on CP threshold suggesting task sensitization. Conclusions Although our results do not suggest that polarity of tDCS targeting left DLPFC differentially modulates tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting left dorsal anterior cingulate cortex showed a trend towards higher mean CP tolerance with cathodal versus anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by DVPRS. Sham-controlled clinical studies are needed. PMID

  17. The significance of organ prolapse in gastroschisis.

    PubMed

    Koehler, Shannon M; Szabo, Aniko; Loichinger, Matt; Peterson, Erika; Christensen, Melissa; Wagner, Amy J

    2017-12-01

    The aim of this study was to evaluate the incidence and importance of organ prolapse (stomach, bladder, reproductive organs) in gastroschisis. This is a retrospective review of gastroschisis patients from 2000 to 2014 at a single tertiary institution. Statistical analysis was performed using a chi-square test, Student's t test, log-rank test, or Cox regression analysis models. All tests were conducted as two-tailed tests, and p-values <0.05 were considered statistically significant. One hundred seventy-one gastroschisis patients were identified. Sixty-nine (40.6%) had at least one prolapsed organ besides bowel. The most commonly prolapsed organs were stomach (n=45, 26.3%), reproductive organs (n=34, 19.9%), and bladder (n=15, 8.8%). Patients with prolapsed organs were more likely to have simple gastroschisis with significant decreases in the rate of atresia and necrosis/perforation. They progressed to earlier enteral feeds, discontinuation of parenteral nutrition, and discharge. Likewise, these patients were less likely to have complications such as central line infections, sepsis, and short gut syndrome. Gastroschisis is typically described as isolated bowel herniation, but a large portion have prolapse of other organs. Prolapsed organs are associated with simple gastroschisis, and improved outcomes most likely due to a larger fascial defect. This may be useful for prenatal and postnatal counseling of families. Case Control/Retrospective Comparative Study. Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Proof-of-Concept Testing of the Passive Cooling System (T-CLIP™) for Solar Thermal Applications at an Elevated Temperature

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Seung Jun; Quintana, Donald L.; Vigil, Gabrielle M.

    2015-11-30

    The Applied Engineering and Technology-1 group (AET-1) at Los Alamos National Laboratory (LANL) conducted the proof-of-concept tests of SolarSPOT LLC’s solar thermal Temperature- Clipper, or T-CLIP™ under controlled thermal conditions using a thermal conditioning unit (TCU) and a custom made environmental chamber. The passive T-CLIP™ is a plumbing apparatus that attaches to a solar thermal collector to limit working fluid temperature and to prevent overheating, since overheating may lead to various accident scenarios. The goal of the current research was to evaluate the ability of the T-CLIP™ to control the working fluid temperature by using its passive cooling mechanism (i.e.more » thermosiphon, or natural circulation) in a small-scale solar thermal system. The assembled environmental chamber that is thermally controlled with the TCU allows one to simulate the various possible weather conditions, which the solar system will encounter. The performance of the T-CLIP™ was tested at two different target temperatures: 1) room temperature (70 °F) and 2) an elevated temperature (130 °F). The current test campaign demonstrated that the T-CLIP™ was able to prevent overheating by thermosiphon induced cooling in a small-scale solar thermal system. This is an important safety feature in situations where the pump is turned off due to malfunction or power outages.« less

  19. Glucose tolerance: hypothesis testing on Malaysian diabetic community.

    PubMed

    Gillani, Syed Wasif; Sari, Yelly Oktavia; Sulaiman, Syed Azhar Syed; Baig, Mirza R

    2014-01-01

    Our study objective was to evaluate glucose tolerance and effecting factors among diabetes patients' with home care program (PHCP) in Malaysian community. A 24-week longitudinal quasi-experimental -single blind - pre/post-test study design was used to assess the effectiveness of a diabetes education program to enhance self-care practices. An attrition rate of 25% implied longitudinal design of the study in the calculation of sample size. Hence the sample size of the study was 106 subjects (53 cases and 53 focus group). The level of significance was set at 0.05. Ethical clearance had been made prior to conducting this study. Of the 109 subjects who met the study-entry criteria, 3 subjects declined to participate due to lack of time and interest. No significant parameters were revealed in the demographic and clinical characteristics of participants who completed the study. Focus group showed significant reduction in HbA1c value with mean 1.1% as compared to cases with a mean 0.06%. Similarly, hypothesis on self-care management suggest significantly improved practices among focus group [M=2.94, SD=2.25] for case group M=0.47, SD=1.36; t[127.64]=-8.23, p≤0.001] with moderate effect size [eta squared=0.06]. Total physical activity was defined as the combination of non-leisure and leisure activities. There was a statistically significant difference for increase in total physical levels between the focus [M=14.01, SD=6.41] and case groups [13.21, SD=5.22; t[148.04]=-3.15, p=0.002] with no difference in the non-leisure activity [p=0.43]. As for the case group, there was no significant difference in SMBG practices from baseline [M=0.70, SD=1.35] to follow-up [M=0.47, SD=1.36, t[72]=0.97, P=0.34] and no relationship was found between the number of blood glucose tests done with demographic or clinical variables. This study offered improved self-care practices and physical activity after PHCP but with problematic dietary care. This might be due to social and cultural habits

  20. Mass Cytometry Analysis Reveals the Landscape and Dynamics of CD32a+ CD4+ T Cells From Early HIV Infection to Effective cART.

    PubMed

    Coindre, Sixtine; Tchitchek, Nicolas; Alaoui, Lamine; Vaslin, Bruno; Bourgeois, Christine; Goujard, Cecile; Avettand-Fenoel, Veronique; Lecuroux, Camille; Bruhns, Pierre; Le Grand, Roger; Beignon, Anne-Sophie; Lambotte, Olivier; Favier, Benoit

    2018-01-01

    CD32a has been proposed as a specific marker of latently HIV-infected CD4 + T cells. However, CD32a was recently found to be expressed on CD4 + T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a + CD4 + T cells during HIV infection. To this end, we analyzed CD32a + CD4 + T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors. We found that CD32a + CD4 + T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive ( N ), central memory ( CM ), and effector/memory ( Eff/Mem ) CD32a + CD4 + T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2 - CD32a + CD4 + T-cell clusters of either the T N , T CM , or T Eff/Mem phenotype were more abundant in healthy individuals. Finally, an activated CD32a + CD4 + T Eff/Mem cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a + CD4 + T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4 + T cells during HIV infection.

  1. Role of Nuclear Pools of Aminoacyl-tRNA Synthetases in tRNA Nuclear Export

    PubMed Central

    Azad, Abul K.; Stanford, David R.; Sarkar, Srimonti; Hopper, Anita K.

    2001-01-01

    Reports of nuclear tRNA aminoacylation and its role in tRNA nuclear export (Lund and Dahlberg, 1998; Sarkar et al., 1999; Grosshans et al., 2000a) have led to the prediction that there should be nuclear pools of aminoacyl-tRNA synthetases. We report that in budding yeast there are nuclear pools of tyrosyl-tRNA synthetase, Tys1p. By sequence alignments we predicted a Tys1p nuclear localization sequence and showed it to be sufficient for nuclear location of a passenger protein. Mutations of this nuclear localization sequence in endogenous Tys1p reduce nuclear Tys1p pools, indicating that the motif is also important for nucleus location. The mutations do not significantly affect catalytic activity, but they do cause defects in export of tRNAs to the cytosol. Despite export defects, the cells are viable, indicating that nuclear tRNA aminoacylation is not required for all tRNA nuclear export paths. Because the tRNA nuclear exportin, Los1p, is also unessential, we tested whether tRNA aminoacylation and Los1p operate in alternative tRNA nuclear export paths. No genetic interactions between aminoacyl-tRNA synthetases and Los1p were detected, indicating that tRNA nuclear aminoacylation and Los1p operate in the same export pathway or there are more than two pathways for tRNA nuclear export. PMID:11359929

  2. Role of nuclear pools of aminoacyl-tRNA synthetases in tRNA nuclear export.

    PubMed

    Azad, A K; Stanford, D R; Sarkar, S; Hopper, A K

    2001-05-01

    Reports of nuclear tRNA aminoacylation and its role in tRNA nuclear export (Lund and Dahlberg, 1998; Sarkar et al., 1999; Grosshans et al., 20001) have led to the prediction that there should be nuclear pools of aminoacyl-tRNA synthetases. We report that in budding yeast there are nuclear pools of tyrosyl-tRNA synthetase, Tys1p. By sequence alignments we predicted a Tys1p nuclear localization sequence and showed it to be sufficient for nuclear location of a passenger protein. Mutations of this nuclear localization sequence in endogenous Tys1p reduce nuclear Tys1p pools, indicating that the motif is also important for nucleus location. The mutations do not significantly affect catalytic activity, but they do cause defects in export of tRNAs to the cytosol. Despite export defects, the cells are viable, indicating that nuclear tRNA aminoacylation is not required for all tRNA nuclear export paths. Because the tRNA nuclear exportin, Los1p, is also unessential, we tested whether tRNA aminoacylation and Los1p operate in alternative tRNA nuclear export paths. No genetic interactions between aminoacyl-tRNA synthetases and Los1p were detected, indicating that tRNA nuclear aminoacylation and Los1p operate in the same export pathway or there are more than two pathways for tRNA nuclear export.

  3. Detailed design of the large-bore 8 T superconducting magnet for the NAFASSY test facility

    NASA Astrophysics Data System (ADS)

    Corato, V.; Affinito, L.; Anemona, A.; Besi Vetrella, U.; Di Zenobio, A.; Fiamozzi Zignani, C.; Freda, R.; Messina, G.; Muzzi, L.; Perrella, M.; Reccia, L.; Tomassetti, G.; Turtù, S.; della Corte, A.

    2015-03-01

    The ‘NAFASSY’ (NAtional FAcility for Superconducting SYstems) facility is designed to test wound conductor samples under high-field conditions at variable temperatures. Due to its unique features, it is reasonable to assume that in the near future NAFASSY will have a preeminent role at the international level in the qualification of long coiled cables in operative conditions. The magnetic system consists of a large warm bore background solenoid, made up of three series-connected grading sections obtained by winding three different Nb3Sn Cable-in-Conduit Conductors. Thanks to the financial support of the Italian Ministry for University and Research the low-field coil is currently under production. The design has been properly modified to allow the system to operate also as a stand-alone facility, with an inner bore diameter of 1144 mm. This magnet is able to provide about 7 T on its axis and about 8 T close to the insert inner radius, giving the possibility of performing a test relevant for large-sized NbTi or medium-field Nb3Sn conductors. The detailed design of the 8 T magnet, including the electro-magnetic, structural and thermo-hydraulic analysis, is here reported, as well as the production status.

  4. Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

    PubMed

    Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

    2015-02-15

    Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p < 0.0001) in Arm A and from 2.23 to 1.99 (p < 0.05) in Arm B. Acanthosis nigricans was significantly reduced in Arm A (13.2% to 5.6%; p < 0.05), and glycosylated-haemoglobin levels were significantly reduced in Arms A (p < 0.005). The percentage of glucose-metabolism abnormalities was reduced, although not significantly. However, the HOMA-IR index was significantly reduced in Arms A (p < 0.0001) and B (p < 0.05), with Arm A showing a significant reduction in the insulinogenic index (p < 0.05). Finally, the disposition index was significantly improved in Arms A (p < 0.0001) and B (p < 0.05). A LGI diet, particularly associated with the use of Policaptil Gel Retard, may reduce weight gain and ameliorate the metabolic syndrome and insulin-resistance parameters in obese children and adolescents with family history of obesity and T2DM.

  5. Genomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals novel recurrent driver mutations

    PubMed Central

    Spinella, Jean-François; Cassart, Pauline; Richer, Chantal; Saillour, Virginie; Ouimet, Manon; Langlois, Sylvie; St-Onge, Pascal; Sontag, Thomas; Healy, Jasmine; Minden, Mark D.; Sinnett, Daniel

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with variable prognosis. It represents 15% of diagnosed pediatric ALL cases and has a threefold higher incidence among males. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p.R35L missense mutation in splicesome factor U2AF1 found in 3 patients and loss of function mutations in the X-linked tumor suppressor genes MED12 (frameshit mutation p.V167fs, splice site mutation g.chrX:70339329T>C, missense mutation p.R1989H) and USP9X (nonsense mutation p.Q117*). In vitro functional studies further supported the putative role of these novel T-ALL genes in driving transformation. U2AF1 p.R35L was shown to induce aberrant splicing of downstream target genes, and shRNA knockdown of MED12 and USP9X was shown to confer resistance to apoptosis following T-ALL relevant chemotherapy drug treatment in Jurkat leukemia cells. Interestingly, nearly 60% of novel candidate driver events were identified among immature T-ALL cases, highlighting the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment. PMID:27602765

  6. Precision Test of the Isobaric Multiplet Mass Equation in the A = 32, T = 2 Quintet

    NASA Astrophysics Data System (ADS)

    Ferrer, R.; Kwiatkowski, A. A.; Bollen, G.; Campbell, C. M.; Folden, C. M., III; Lincoln, D.; Morrissey, D. J.; Pang, G. K.; Prinke, A.; Savory, J.; Schwarz, S.

    2008-10-01

    Masses of the radionuclides ^32,33Si and ^34P and of the stable nuclide ^32S have been measured with the Low Energy Beam and Ion Trap (LEBIT) Penning trap mass spectrometer. Relative mass uncertainties of 3 x 10-8 and better have been achieved. The measured mass value of ^32Si differs from the literature value [1,2] by four standard deviations. The precise mass determination of ^32Si and ^32S have been employed to test the isobaric multiplet mass equation for the A = 32, T= 2 isospin quintet. The experimental results indicate a significant deviation from the quadratic form. This work has been supported by Michigan State University, the NSF under contract number PHY- 0606007, and the DOE under the contract DE-FG02-00ER41144. References: 1. G. Audi, A.H. Wapstra, and C. Thibault, Nucl. Phys. A729 (2003) 337 2. A. Paul, S. R"ottger, A. Zimbal, and U. Keyser, Hyperfine Interact. 132 (2001) 189

  7. Indirect antiglobulin test-crossmatch using low-ionic-strength saline-albumin enhancement medium and reduced incubation time: effectiveness in the detection of most clinically significant antibodies and impact on blood utilization.

    PubMed

    Dinardo, C L; Bonifácio, S L; Mendrone, A

    2014-01-01

    Indirect antiglobulin test-crossmatch (IAT-XM) using enhancement media such as low-ionic-strength saline (LISS) and polyethylene glycol (PEG) usually requires 15 minutes of incubation. These methods are necessary when testing samples from blood recipients who have a higher risk of alloimmunization. In emergency situations, IAT-XM can be time-consuming and can influence presurgery routine, resulting in more red blood cell (RBC) units being tested and stored to avoid the transfusion of uncrossmatched ones. The objective of this study was to evaluate the performance of a LISS-albumin enhancer to intensify antigen-antibody reaction after 5 minutes of 37oC incubation and compare this performance with that of other enhancers, gel, and conventional tube testing. Second, the study evaluated the impact of this method's implementation in the C:T ratio (crossmatched to transfused RBC units) of a transfusion laboratory. Ninety serum samples containing alloantibodies of potential clinical significance were tested against phenotyped RBCs using four different methods: (1) tube with LISS-albumin enhancer (5 minutes of incubation), (2) tube with LISS-albumin and PEG (15 minutes of incubation), (3) gel, and (4) conventional tube method (60 minutes of incubation). In parallel, the study compared the C:T ratio of a tertiary-hospital transfusion laboratory in two different periods: 3 months before and 3 months after the implementation of the 5-minute IAT-XM protocol. The use of LISS-albumin with 5 minutes of incubation exhibited the same performance as LISS-albumin, PEG, and gel with 15 minutes of incubation. Conventional tube method results were equally comparable, but reactions were significantly less intense, except for anti-c (p = 0.406). Accuracy was 100 percent for all selected methods. After the implementation of the 5-minute IAT-XM protocol, the C:T ratio fell from 2.74 to 1.29 (p < 0.001). IAT-XM can have its incubation time reduced to 5 minutes with the use of LISS

  8. Microarc Oxidation Coating Combined with Surface Pore-Sealing Treatment Enhances Corrosion Fatigue Performance of 7075-T7351 Al Alloy in Different Media

    PubMed Central

    Yang, Hui-Hui; Wang, Xi-Shu; Wang, Ya-Ming; Wang, Yan-Ling; Zhang, Zhi-Hao

    2017-01-01

    Rotating bending fatigue tests have been performed to evaluate the corrosion fatigue performance and its influence factors of 7075-T7351 Al alloy in different media, namely air and a 5.0 wt % NaCl aqueous solution. All samples were coated by microarc oxidation (MAO) coating technology; some samples were followed by an epoxy resin pore-sealing treatment. Microscopic analyses of the surfaces and fracture cross-sections of samples were carried out. The results reveal that the sample with a MAO coating of 10 μm thickness and pore-sealing treatment by epoxy resin possesses optimal corrosion fatigue performance in the different media. The MAO coating with a pore-sealing treatment significantly improves the corrosion fatigue limit of 7075-T7351 Al alloy. PMID:28772970

  9. Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

    PubMed Central

    Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

    2015-01-01

    Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. Conclusion Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis

  10. Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure.

    PubMed

    Ishak, Siti Nor Hasmah; Aris, Sayangku Nor Ariati Mohamad; Halim, Khairul Bariyyah Abd; Ali, Mohd Shukuri Mohamad; Leow, Thean Chor; Kamarudin, Nor Hafizah Ahmad; Masomian, Malihe; Rahman, Raja Noor Zaliha Raja Abd

    2017-09-25

    Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition.

  11. Comprehensive evaluation of the Estrogen Receptor Alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population

    PubMed Central

    Keene, Keith L.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Leak, Tennille S.; Perlegas, Peter S.; Langefeld, Carl D.; Herrington, David M.; Freedman, Barry I.; Rich, Stephen S.; Bowden, Donald W.; Sale, Michèle M.

    2009-01-01

    We previously investigated the estrogen receptor α gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and type 2 diabetes and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and End Stage Renal Disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a χ2 statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P< 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P=0.000291, adjusted P=0.0289), and intron 4 SNPs rs1569788 (nominal P=0.000754, adjusted P=0.0278) and rs9340969 (nominal P=0.00109, adjusted P=0.0467) remained significant at experimentwise error rate (EER) P<0.05 for the dominant class of tests. Twenty-three of the thirty-one associated SNPs cluster within the intron 4-intron 6 region. Gender stratification revealed nominal evidence for association with 35 SNPs in females (352 cases; 306 controls) and seven SNPs in males (225 cases; 290 controls). We have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy. PMID:18305958

  12. Study of the efficiency of transplantation of human neural stem cells to rats with spinal trauma: the use of functional load tests and BBB test.

    PubMed

    Lebedev, S V; Karasev, A V; Chekhonin, V P; Savchenko, E A; Viktorov, I V; Chelyshev, Yu A; Shaimardanova, G F

    2010-09-01

    Human ensheating neural stem cells of the olfactory epithelium were transplanted to adult male rats immediately after contusion trauma of the spinal cord at T9 level rostrally and caudally to the injury. Voluntary movements (by a 21-point BBB scale), rota-rod performance, and walking along a narrowing beam were monitored weekly over 60 days. In rats receiving cell transplantation, the mean BBB score significantly increased by 11% by the end of the experiment. The mean parameters of load tests also regularly surpassed the corresponding parameters in controls. The efficiency of transplantation (percent of animals with motor function recovery parameters surpassing the corresponding mean values in the control groups) was 62% by the state of voluntary motions, 37% by the rota-rod test, and 32% by the narrowing beam test. Morphometry revealed considerable shrinking of the zone of traumatic damage in the spinal cord and activation of posttraumatic remyelination in animals receiving transplantation of human neural stem cells.

  13. Functional ankle instability as a risk factor for osteoarthritis: using T2-mapping to analyze early cartilage degeneration in the ankle joint of young athletes.

    PubMed

    Golditz, T; Steib, S; Pfeifer, K; Uder, M; Gelse, K; Janka, R; Hennig, F F; Welsch, G H

    2014-10-01

    The aim of this study was to investigate, using T2-mapping, the impact of functional instability in the ankle joint on the development of early cartilage damage. Ethical approval for this study was provided. Thirty-six volunteers from the university sports program were divided into three groups according to their ankle status: functional ankle instability (FAI, initial ankle sprain with residual instability); ankle sprain Copers (initial sprain, without residual instability); and controls (without a history of ankle injuries). Quantitative T2-mapping magnetic resonance imaging (MRI) was performed at the beginning ('early-unloading') and at the end ('late-unloading') of the MR-examination, with a mean time span of 27 min. Zonal region-of-interest T2-mapping was performed on the talar and tibial cartilage in the deep and superficial layers. The inter-group comparisons of T2-values were analyzed using paired and unpaired t-tests. Statistical analysis of variance was performed. T2-values showed significant to highly significant differences in 11 of 12 regions throughout the groups. In early-unloading, the FAI-group showed a significant increase in quantitative T2-values in the medial, talar regions (P = 0.008, P = 0.027), whereas the Coper-group showed this enhancement in the central-lateral regions (P = 0.05). Especially the comparison of early-loading to late-unloading values revealed significantly decreasing T2-values over time laterally and significantly increasing T2-values medially in the FAI-group, which were not present in the Coper- or control-group. Functional instability causes unbalanced loading in the ankle joint, resulting in cartilage alterations as assessed by quantitative T2-mapping. This approach can visualize and localize early cartilage abnormalities, possibly enabling specific treatment options to prevent osteoarthritis in young athletes. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. An evaluation of the pressure proof test concept for thin sheet 2024-T3

    NASA Technical Reports Server (NTRS)

    Dawicke, D. S.; Poe, C. C., Jr.; Newman, J. C., Jr.; Harris, C. E.

    1990-01-01

    The concept of pressure proof testing of fuselage structures with fatigue cracks to insure structural integrity was evaluated from a fracture mechanics viewpoint. A generic analytical and experimental investigation was conducted on uniaxially loaded flat panels with crack configurations and stress levels typical of longitudinal lap-splice joints in commercial transport aircraft fuselage. The results revealed that the remaining fatigue life after a proof test was longer than that without the proof test because of crack growth retardation due to increased crack closure. However, based on a crack length that is slightly less than the critical value at the maximum proof test stress, the minimum assured life or proof test interval must be no more than 550 pressure cycles for a 1.33 proof factor and 1530 pressure cycles for a 1.5 proof factor to prevent in-flight failures.

  15. An evaluation of the pressure proof test concept for thin sheet 2024-T3

    NASA Technical Reports Server (NTRS)

    Dawicke, D. S.; Poe, C. C., Jr.; Newman, James C., Jr.; Harris, Charles E.

    1990-01-01

    The concept of pressure proof testing of fuselage structures with fatigue cracks to insure structural integrity was evaluated from a fracture mechanics viewpoint. A generic analytical and experimental investigation was conducted on uniaxially loaded flat panels with crack configurations and stress levels typical of longitudinal lap splice joints in commercial transport aircraft fuselages. The results revealed that the remaining fatigue life after a proof test was longer than that without the proof test because of crack growth retardation due to increased crack closure. However, based on a crack length that is slightly less than the critical value at the maximum proof test stress, the minimum assured life or proof test interval must be no more than 550 pressure cycles for a 1.33 proof factor and 1530 pressure cycles for a 1.5 proof factor to prevent in-flight failures.

  16. In routine UK hospital practice T-SPOT.TB™ is useful in some patients with a modest pre-test probability of active tuberculosis.

    PubMed

    Turtle, Lance; Kemp, Tim; Davies, Geraint R; Squire, S Bertie; Beeching, Nick J; Beadsworth, Michael B J

    2012-06-01

    to assess the usefulness of the T-SPOT.TB™ interferon-gamma release assay (IGRA), as used in a regional hospital infectious diseases unit in Northwest England, for the diagnosis of active tuberculosis. Retrospective case series. T-SPOT.TB™ test was applied to a group of 64 patients, 20 of whom had tuberculosis (mostly extra-pulmonary tuberculosis). The T-SPOT.TB™ test had a sensitivity of 83.3% and a specificity of 75% for the diagnosis of active tuberculosis, compared with culture. A positive IGRA approximately doubled the pre-test probability of disease from 0.23 to 0.5. This doubling of probability was true regardless of HIV status, though for HIV+ patients the sensitivity was lower (sensitivity 66.7%, post test probability 0.4 for a positive IGRA result). When extrapolated to the local population the test was most useful for exclusion of disease; post test probability 0.006 (or 1 in 167) for a negative IGRA result. Although it can add weight to a clinical diagnosis, T-SPOT.TB™ assay is not reliable for the diagnosis of active tuberculosis in a real world setting where the test is often used in patients with smear negative or extra-pulmonary disease. The test is useful for ruling out disease in HIV negative patients. Copyright © 2012. Published by Elsevier B.V.

  17. Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment.

    PubMed

    Li, Weihua; Qiu, Tian; Guo, Lei; Ling, Yun; Gao, Yibo; Ying, Jianming; He, Jie

    2018-06-01

    Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients. T790M always coexisted with a sensitizing EGFR mutation. Primary T790M more commonly coexisted with L858R, whereas acquired T790M was more likely to coexist with exon 19 deletions. Moreover, next-generation sequencing (NGS) showed that concomitant sensitizing EGFR and primary T790M mutant allele frequencies (MAFs) were highly concordant, but acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs. Sixteen acquired T790M-mutant patients received osimertinib. The median progression-free survival (PFS) was 8.1 months. Four primary T790M-mutant patients received osimertinib and the median PFS was 8.0 months. Together, our study demonstrates that primary and acquired T790M-mutant patients show distinct differences in some clinical and molecular characteristics, but may both respond to osimertinib treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.

    PubMed

    Almanzar, Giovanni; Schmalzing, Marc; Trippen, Raimund; Höfner, Kerstin; Weißbrich, Benedikt; Geissinger, Eva; Meyer, Thomas; Liese, Johannes; Tony, Hans-Peter; Prelog, Martina

    2016-04-01

    Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA). Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients. Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls. Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The clinical significance of 10-m walk test standardizations in Parkinson's disease.

    PubMed

    Lindholm, Beata; Nilsson, Maria H; Hansson, Oskar; Hagell, Peter

    2018-06-06

    The 10-m walk test (10MWT) is a widely used measure of gait speed in Parkinson's disease (PD). However, it is unclear if different standardizations of its conduct impact test results. We examined the clinical significance of two aspects of the standardization of the 10MWT in mild PD: static vs. dynamic start, and a single vs. repeated trials. Implications for fall prediction were also explored. 151 people with PD (mean age and PD duration, 68 and 4 years, respectively) completed the 10MWT in comfortable gait speed with static and dynamic start (two trials each), and gait speed (m/s) was recorded. Participants then registered all prospective falls for 6 months. Absolute mean differences between outcomes from the various test conditions ranged between 0.016 and 0.040 m/s (effect sizes, 0.06-0.14) with high levels of agreement (intra-class correlation coefficients, 0.932-0.987) and small standard errors of measurement (0.032-0.076 m/s). Receiver operating characteristic curves showed similar discriminate abilities for prediction of future falls across conditions (areas under curves, 0.70-0.73). Cut-off points were estimated at 1.1-1.2 m/s. Different 10MWT standardizations yield very similar results, suggesting that there is no practical need for an acceleration distance or repeated trials when conducting this test in mild PD.

  20. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

    PubMed

    Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

    2016-08-16

    Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. MASH TL-3 crash testing and evaluation of the TxDOT T631 Bridge Rail.

    DOT National Transportation Integrated Search

    2016-07-01

    The Texas Type T631 bridge rail was developed as a low-cost, flexible bridge rail system for TL-2 : applications. Many of the features used for the system tested at MwRSF for TL-3 were incorporated into the : design developed for this project for MAS...

  2. Novel method to assess gastric emptying in humans: the Pellet Gastric Emptying Test

    NASA Technical Reports Server (NTRS)

    Choe, S. Y.; Neudeck, B. L.; Welage, L. S.; Amidon, G. E.; Barnett, J. L.; Amidon, G. L.

    2001-01-01

    To further validate the Pellet Gastric Emptying Test (PGET) as a marker of gastric emptying, a randomized, four-way crossover study was conducted with 12 healthy subjects. The study consisted of oral co-administration of enteric coated caffeine (CAFF) and acetaminophen (APAP) pellets in four treatment phases: Same Size (100 kcal), Fasted, Small Liquid Meal (100 kcal), and Standard Meal (847 kcal). The time of first appearance of measurable drug marker in plasma, t(initial), was taken as the emptying time for the markers. Co-administration of same size enteric coated pellets of CAFF and APAP (0.7 mm in diameter) revealed no statistically significant differences in t(initial) values indicating that emptying was dependent only on size and not on chemical make-up of the pellets. Co-administration of different size pellets indicated that the smaller 0.7-mm diameter (CAFF) pellets were emptied and absorbed significantly earlier than the larger 3.6-mm diameter (APAP) pellets with both the Small Liquid Meal (by 35 min) and the Standard Meal (by 33 min) (P<0.05). The differences in emptying of the pellets were not significant in the Fasted Phase. The results suggest that the pellet gastric emptying test could prove useful in monitoring changes in transit times in the fasted and fed states and their impact on drug absorption.

  3. Working memory capacity differentially influences responses to tDCS and HD-tDCS in a retro-cue task.

    PubMed

    Gözenman, Filiz; Berryhill, Marian E

    2016-08-26

    There is growing interest in non-invasive brain stimulation techniques. A drawback is that the relationship between stimulation and cognitive outcomes for various tasks are unknown. Transcranial direct current stimulation (tDCS) provides diffuse current spread, whereas high-definition tDCS (HD-tDCS) provides more targeted current. The direction of behavioral effects after tDCS can be difficult to predict in cognitive realms such as attention and working memory (WM). Previously, we showed that in low and high WM capacity groups tDCS modulates performance in nearly equal and opposite directions on a change detection task, with improvement for the high capacity participants alone. Here, we used the retro-cue paradigm to test attentional shifting among items in WM to investigate whether WM capacity (WMC) predicted different behavioral consequences during anodal tDCS or HD-tDCS to posterior parietal cortex (PPC). In two experiments, with 24 participants each, we used different stimulus categories (colored circles, letters) and stimulation sites (right, left PPC). The results showed a significant (Experiment 1) or trending (Experiment 2) WMC x stimulation interaction. Compared to tDCS, after HD-tDCS the retro-cueing benefit was significantly greater for the low WMC group but numerically worse for the high WMC group. These data highlight the importance of considering group differences when using non-invasive neurostimulation techniques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

    PubMed Central

    Rucevic, Marijana; Kourjian, Georgio; Boucau, Julie; Blatnik, Renata; Garcia Bertran, Wilfredo; Berberich, Matthew J.; Walker, Bruce D.; Riemer, Angelika B.

    2016-01-01

    ABSTRACT Despite the critical role of epitope presentation for immune recognition, we still lack a comprehensive definition of HIV peptides presented by HIV-infected cells. Here we identified 107 major histocompatibility complex (MHC)-bound HIV peptides directly from the surface of live HIV-transfected 293T cells, HIV-infected B cells, and primary CD4 T cells expressing a variety of HLAs. The majority of peptides were 8 to 12 amino acids (aa) long and mostly derived from Gag and Pol. The analysis of the total MHC-peptidome and of HLA-A02-bound peptides identified new noncanonical HIV peptides of up to 16 aa that could not be predicted by HLA anchor scanning and revealed an heterogeneous surface peptidome. Nested sets of surface HIV peptides included optimal and extended HIV epitopes and peptides partly overlapping or distinct from known epitopes, revealing new immune responses in HIV-infected persons. Surprisingly, in all three cell types, a majority of Gag peptides derived from p15 rather than from the most immunogenic p24. The cytosolic degradation of peptide precursors in corresponding cells confirmed the generation of identified surface-nested peptides. Cytosolic degradation revealed peptides commonly produced in all cell types and displayed by various HLAs, peptides commonly produced in all cell types and selectively displayed by specific HLAs, and peptides produced in only one cell type. Importantly, we identified areas of proteins leading to common presentations of noncanonical peptides by several cell types with distinct HLAs. These peptides may benefit the design of immunogens, focusing T cell responses on relevant markers of HIV infection in the context of HLA diversity. IMPORTANCE The recognition of HIV-infected cells by immune T cells relies on the presentation of HIV-derived peptides by diverse HLA molecules at the surface of cells. The landscape of HIV peptides displayed by HIV-infected cells is not well defined. Considering the diversity of HLA

  5. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain.

    PubMed

    Zhao, Yunjie; Zeng, Chen; Massiah, Michael A

    2015-01-01

    The zinc-binding Bbox1 domain in protein MID1, a member of the TRIM family of proteins, facilitates the ubiquitination of the catalytic subunit of protein phosphatase 2A and alpha4, a protein regulator of PP2A. The natural mutation of residue A130 to a valine or threonine disrupts substrate recognition and catalysis. While NMR data revealed the A130T mutant Bbox1 domain failed to coordinate both structurally essential zinc ions and resulted in an unfolded structure, the unfolding mechanism is unknown. Principle component analysis revealed that residue A130 served as a hinge point between the structured β-strand-turn-β-strand (β-turn-β) and the lasso-like loop sub-structures that constitute loop1 of the ββα-RING fold that the Bbox1 domain adopts. Backbone RMSD data indicate significant flexibility and departure from the native structure within the first 5 ns of the molecular dynamics (MD) simulation for the A130V mutant (>6 Å) and after 30 ns for A130T mutant (>6 Å). Overall RMSF values were higher for the mutant structures and showed increased flexibility around residues 125 and 155, regions with zinc-coordinating residues. Simulated pKa values of the sulfhydryl group of C142 located near A130 suggested an increased in value to ~9.0, paralleling the increase in the apparent dielectric constants for the small cavity near residue A130. Protonation of the sulfhydryl group would disrupt zinc-coordination, directly contributing to unfolding of the Bbox1. Together, the increased motion of residues of loop 1, which contains four of the six zinc-binding cysteine residues, and the increased pKa of C142 could destabilize the structure of the zinc-coordinating residues and contribute to the unfolding.

  6. Efficacy of Cyto-Chex blood preservative for delayed manual CD4 testing using Dynal T4 Quant CD4 test among HIV-infected persons in Zambia.

    PubMed

    Truett, April A; Letizia, Andrew; Malyangu, Evans; Sinyangwe, Frank; Morales, Brandi N; Crum, Nancy F; Crowe, Suzanne M

    2006-02-01

    Manual CD4 tests such as Dynal T4 Quant (Dynabeads, Dynal Biotech, Oslo, Norway) are less expensive alternatives to flow cytometry in resource-limited countries. Whereas blood preservatives have proven useful for stabilizing blood samples to allow delayed CD4 testing by flow cytometry, they have not been verified for manual tests. A method for preservation of blood prior to manual CD4 testing is needed for long-distance transport or sample batching. Blood from HIV-positive Zambian military beneficiaries was mixed (1:1) with Cyto-Chex (Streck Laboratories, La Vista, NE) blood preservative, and the blood was stored at refrigerated, ambient, and incubator (37 degrees C) temperatures prior to Dynabeads CD4 testing at 0, 3, 6, and 9 days after collection. Baseline flow cytometry and Dynabeads testing without preservative were performed for comparison. Twenty-seven patient samples were analyzed. Dynabeads vs. flow cytometry had a correlation coefficient (r) of 0.84. There was excellent correlation (r = 0.96) between baseline Dynabeads testing and Cyto-Chex-preserved samples. Refrigerated samples showed strong correlation with baseline Dynabeads (r = 0.93-0.95) on days 3, 6, and 9 without decline in CD4 count (P = 0.73). Samples stored at ambient temperature yielded inferior results (r = 0.76-0.81), with a significant decline in CD4 count by day 3 (P < 0.001). The incubator arm had especially poor correlation (r = 0.30-0.49). Addition of Cyto-Chex to peripheral blood (1:1) adequately preserves refrigerated blood samples for up to 9 days for subsequent testing with Dynabeads CD4 test. Cyto-Chex, however, cannot be recommended for delayed Dynabeads CD4 testing with storage at 37 degrees C or ambient temperatures in tropical areas similar to the site of this study.

  7. Comparison of biochemical cartilage imaging techniques at 3 T MRI.

    PubMed

    Rehnitz, C; Kupfer, J; Streich, N A; Burkholder, I; Schmitt, B; Lauer, L; Kauczor, H-U; Weber, M-A

    2014-10-01

    To prospectively compare chemical-exchange saturation-transfer (CEST) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping to assess the biochemical cartilage properties of the knee. Sixty-nine subjects were prospectively included (median age, 42 years; male/female = 32/37) in three cohorts: 10 healthy volunteers, 40 patients with clinically suspected cartilage lesions, and 19 patients about 1 year after microfracture therapy. T2 mapping, dGEMRIC, and CEST were performed at a 3 T MRI unit using a 15-channel knee coil. Parameter maps were evaluated using region-of-interest analysis of healthy cartilage, areas of chondromalacia and repair tissue. Differentiation of damaged from healthy cartilage was assessed using receiver-operating characteristic (ROC) analysis. Chondromalacia grade 2-3 had significantly higher CEST values (P = 0.001), lower dGEMRIC (T1-) values (P < 0.001) and higher T2 values (P < 0.001) when compared to the normal appearing cartilage. dGEMRIC and T2 mapping correlated moderately negative (Spearman coefficient r = -0.56, P = 0.0018) and T2 mapping and CEST moderately positive (r = 0.5, P = 0.007), while dGEMRIC and CEST did not significantly correlate (r = -0.311, P = 0.07). The repair tissue revealed lower dGEMRIC values (P < 0.001) and higher CEST values (P < 0.001) with a significant negative correlation (r = -0.589, P = 0.01), whereas T2 values were not different (P = 0.54). In healthy volunteers' cartilage, CEST and dGEMRIC showed moderate positive correlation (r = 0.56), however not reaching significance (P = 0.09). ROC-analysis demonstrated non-significant differences of T2 mapping vs CEST (P = 0.14), CEST vs dGEMRIC (P = 0.89), and T2 mapping vs dGEMRIC (P = 0.12). CEST is able to detect normal and damaged cartilage and is non-inferior in distinguishing both when compared to dGEMRIC and T2 mapping. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. Comprehensive Survey of miRNA-mRNA Interactions Reveals That Ccr7 and Cd247 (CD3 zeta) are Posttranscriptionally Controlled in Pancreas Infiltrating T Lymphocytes of Non-Obese Diabetic (NOD) Mice.

    PubMed

    Fornari, Thais A; Donate, Paula B; Assis, Amanda F; Macedo, Claudia; Sakamoto-Hojo, Elza T; Donadi, Eduardo A; Passos, Geraldo A

    2015-01-01

    In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4+ and CD8+ T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown. In this study, we postulated that miRNAs are differentially expressed during this period and that these miRNAs can interact with mRNAs involved in auto-reactivity during the progression of insulitis. To test this hypothesis, we used NOD mice to perform, for the first time, a comprehensive survey of miRNA and mRNA expression as thymocytes mature into peripheral CD3+ T lymphocytes and, subsequently, into PILs. Reconstruction of miRNA-mRNA interaction networks for target prediction revealed the participation of a large set of miRNAs that regulate mRNA targets related to apoptosis, cell adhesion, cellular regulation, cellular component organization, cellular processes, development and the immune system, among others. The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of how the lack of immune homeostasis and the emergence of autoimmunity (e.g., T1D) can be associated with the decreased activity of Ccr7 or Cd247, as previously observed in NOD mice. We demonstrate that these mRNAs are controlled at the posttranscriptional level in PILs.

  9. Comprehensive Survey of miRNA-mRNA Interactions Reveals That Ccr7 and Cd247 (CD3 zeta) are Posttranscriptionally Controlled in Pancreas Infiltrating T Lymphocytes of Non-Obese Diabetic (NOD) Mice

    PubMed Central

    Macedo, Claudia; Sakamoto-Hojo, Elza T.; Donadi, Eduardo A.; Passos, Geraldo A.

    2015-01-01

    In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4+ and CD8+ T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown. In this study, we postulated that miRNAs are differentially expressed during this period and that these miRNAs can interact with mRNAs involved in auto-reactivity during the progression of insulitis. To test this hypothesis, we used NOD mice to perform, for the first time, a comprehensive survey of miRNA and mRNA expression as thymocytes mature into peripheral CD3+ T lymphocytes and, subsequently, into PILs. Reconstruction of miRNA-mRNA interaction networks for target prediction revealed the participation of a large set of miRNAs that regulate mRNA targets related to apoptosis, cell adhesion, cellular regulation, cellular component organization, cellular processes, development and the immune system, among others. The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of how the lack of immune homeostasis and the emergence of autoimmunity (e.g., T1D) can be associated with the decreased activity of Ccr7 or Cd247, as previously observed in NOD mice. We demonstrate that these mRNAs are controlled at the posttranscriptional level in PILs. PMID:26606254

  10. Significant lexical relationships

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pedersen, T.; Kayaalp, M.; Bruce, R.

    Statistical NLP inevitably deals with a large number of rare events. As a consequence, NLP data often violates the assumptions implicit in traditional statistical procedures such as significance testing. We describe a significance test, an exact conditional test, that is appropriate for NLP data and can be performed using freely available software. We apply this test to the study of lexical relationships and demonstrate that the results obtained using this test are both theoretically more reliable and different from the results obtained using previously applied tests.

  11. A Historical Evaluation of the U12t Tunnel, Nevada Test Site, Nye County, Nevada, Volume 1 of 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Drollinger, Harold; Jones, Robert C.; Thomas F. Bullard

    2009-02-01

    This report presents a historical evaluation of the U12t Tunnel on the Nevada Test Site in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office and the U.S. Department of Defense, Defense Threat Reduction Agency (DTRA). The U12t Tunnel is one of a series of tunnels used for underground nuclear weapons effects tests on the east side of Rainier and Aqueduct Mesas. Six nuclear weapons effects tests, Mint Leaf, Diamond Sculls, Husky Pup, Midas Myth/Milagro, Mighty Oak, and Mission Ghost, and onemore » high explosive test, SPLAT, were conducted within the U12t Tunnel from 1970 to 1987. All six of the nuclear weapons effects tests and the high explosive test were sponsored by DTRA. Two conventional weapons experiments, Dipole Knight and Divine Eagle, were conducted in the tunnel portal area in 1997 and 1998. These experiments were sponsored by the Defense Special Weapons Agency. The U12t Tunnel complex is composed of the Portal and Mesa Areas and includes an underground tunnel with a main access drift and nine primary drifts, a substantial tailings pile fronting the tunnel portal, a series of discharge ponds downslope of the tailings pile, and two instrumentation trailer parks and 16 drill holes on top of Aqueduct Mesa. A total of 89 cultural features were recorded: 54 at the portal and 35 on the mesa. In the Portal Area, cultural features are mostly concrete pads and building foundations; other features include the portal, rail lines, the camel back, ventilation and cooling system components, communication equipment, and electrical equipment. On the mesa are drill holes, a few concrete pads, a loading ramp, and electrical equipment.« less

  12. A Historical Evaluation of the U12t Tunnel, Nevada Test Site, Nye County, Nevada, Volume 5 of 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harold Drollinger; Robert C. Jones; and Thomas F. Bullard

    2009-02-01

    This report presents a historical evaluation of the U12t Tunnel on the Nevada Test Site in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office and the U.S. Department of Defense, Defense Threat Reduction Agency (DTRA). The U12t Tunnel is one of a series of tunnels used for underground nuclear weapons effects tests on the east side of Rainier and Aqueduct Mesas. Six nuclear weapons effects tests, Mint Leaf, Diamond Sculls, Husky Pup, Midas Myth/Milagro, Mighty Oak, and Mission Ghost, and onemore » high explosive test, SPLAT, were conducted within the U12t Tunnel from 1970 to 1987. All six of the nuclear weapons effects tests and the high explosive test were sponsored by DTRA. Two conventional weapons experiments, Dipole Knight and Divine Eagle, were conducted in the tunnel portal area in 1997 and 1998. These experiments were sponsored by the Defense Special Weapons Agency. The U12t Tunnel complex is composed of the Portal and Mesa Areas and includes an underground tunnel with a main access drift and nine primary drifts, a substantial tailings pile fronting the tunnel portal, a series of discharge ponds downslope of the tailings pile, and two instrumentation trailer parks and 16 drill holes on top of Aqueduct Mesa. A total of 89 cultural features were recorded: 54 at the portal and 35 on the mesa. In the Portal Area, cultural features are mostly concrete pads and building foundations; other features include the portal, rail lines, the camel back, ventilation and cooling system components, communication equipment, and electrical equipment. On the mesa are drill holes, a few concrete pads, a loading ramp, and electrical equipment.« less

  13. A Historical Evaluation of the U12t Tunnel, Nevada Test Site, Nye County, Nevada, Volume 6 of 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harold Drollinger; Robert C. Jones; and Thomas F. Bullard

    2009-02-01

    This report presents a historical evaluation of the U12t Tunnel on the Nevada Test Site in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office and the U.S. Department of Defense, Defense Threat Reduction Agency (DTRA). The U12t Tunnel is one of a series of tunnels used for underground nuclear weapons effects tests on the east side of Rainier and Aqueduct Mesas. Six nuclear weapons effects tests, Mint Leaf, Diamond Sculls, Husky Pup, Midas Myth/Milagro, Mighty Oak, and Mission Ghost, and onemore » high explosive test, SPLAT, were conducted within the U12t Tunnel from 1970 to 1987. All six of the nuclear weapons effects tests and the high explosive test were sponsored by DTRA. Two conventional weapons experiments, Dipole Knight and Divine Eagle, were conducted in the tunnel portal area in 1997 and 1998. These experiments were sponsored by the Defense Special Weapons Agency. The U12t Tunnel complex is composed of the Portal and Mesa Areas and includes an underground tunnel with a main access drift and nine primary drifts, a substantial tailings pile fronting the tunnel portal, a series of discharge ponds downslope of the tailings pile, and two instrumentation trailer parks and 16 drill holes on top of Aqueduct Mesa. A total of 89 cultural features were recorded: 54 at the portal and 35 on the mesa. In the Portal Area, cultural features are mostly concrete pads and building foundations; other features include the portal, rail lines, the camel back, ventilation and cooling system components, communication equipment, and electrical equipment. On the mesa are drill holes, a few concrete pads, a loading ramp, and electrical equipment.« less

  14. A Historical Evaluation of the U12t Tunnel, Nevada Test Site, Nye County, Nevada, Volume 3 of 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harold Drollinger; Robert C. Jones; and Thomas F. Bullard

    2009-02-01

    This report presents a historical evaluation of the U12t Tunnel on the Nevada Test Site in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office and the U.S. Department of Defense, Defense Threat Reduction Agency (DTRA). The U12t Tunnel is one of a series of tunnels used for underground nuclear weapons effects tests on the east side of Rainier and Aqueduct Mesas. Six nuclear weapons effects tests, Mint Leaf, Diamond Sculls, Husky Pup, Midas Myth/Milagro, Mighty Oak, and Mission Ghost, and onemore » high explosive test, SPLAT, were conducted within the U12t Tunnel from 1970 to 1987. All six of the nuclear weapons effects tests and the high explosive test were sponsored by DTRA. Two conventional weapons experiments, Dipole Knight and Divine Eagle, were conducted in the tunnel portal area in 1997 and 1998. These experiments were sponsored by the Defense Special Weapons Agency. The U12t Tunnel complex is composed of the Portal and Mesa Areas and includes an underground tunnel with a main access drift and nine primary drifts, a substantial tailings pile fronting the tunnel portal, a series of discharge ponds downslope of the tailings pile, and two instrumentation trailer parks and 16 drill holes on top of Aqueduct Mesa. A total of 89 cultural features were recorded: 54 at the portal and 35 on the mesa. In the Portal Area, cultural features are mostly concrete pads and building foundations; other features include the portal, rail lines, the camel back, ventilation and cooling system components, communication equipment, and electrical equipment. On the mesa are drill holes, a few concrete pads, a loading ramp, and electrical equipment.« less

  15. A Historical Evaluation of the U12t Tunnel, Nevada Test Site, Nye County, Nevada, Volume 2 of 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harold Drollinger; Robert C. Jones; and Thomas F. Bullard

    2009-02-01

    This report presents a historical evaluation of the U12t Tunnel on the Nevada Test Site in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office and the U.S. Department of Defense, Defense Threat Reduction Agency (DTRA). The U12t Tunnel is one of a series of tunnels used for underground nuclear weapons effects tests on the east side of Rainier and Aqueduct Mesas. Six nuclear weapons effects tests, Mint Leaf, Diamond Sculls, Husky Pup, Midas Myth/Milagro, Mighty Oak, and Mission Ghost, and onemore » high explosive test, SPLAT, were conducted within the U12t Tunnel from 1970 to 1987. All six of the nuclear weapons effects tests and the high explosive test were sponsored by DTRA. Two conventional weapons experiments, Dipole Knight and Divine Eagle, were conducted in the tunnel portal area in 1997 and 1998. These experiments were sponsored by the Defense Special Weapons Agency. The U12t Tunnel complex is composed of the Portal and Mesa Areas and includes an underground tunnel with a main access drift and nine primary drifts, a substantial tailings pile fronting the tunnel portal, a series of discharge ponds downslope of the tailings pile, and two instrumentation trailer parks and 16 drill holes on top of Aqueduct Mesa. A total of 89 cultural features were recorded: 54 at the portal and 35 on the mesa. In the Portal Area, cultural features are mostly concrete pads and building foundations; other features include the portal, rail lines, the camel back, ventilation and cooling system components, communication equipment, and electrical equipment. On the mesa are drill holes, a few concrete pads, a loading ramp, and electrical equipment.« less

  16. A Historical Evaluation of the U12t Tunnel, Nevada Test Site, Nye County, Nevada, Volume 4 of 6

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harold Drollinger; Robert C. Jones; and Thomas F. Bullard

    2009-02-01

    This report presents a historical evaluation of the U12t Tunnel on the Nevada Test Site in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office and the U.S. Department of Defense, Defense Threat Reduction Agency (DTRA). The U12t Tunnel is one of a series of tunnels used for underground nuclear weapons effects tests on the east side of Rainier and Aqueduct Mesas. Six nuclear weapons effects tests, Mint Leaf, Diamond Sculls, Husky Pup, Midas Myth/Milagro, Mighty Oak, and Mission Ghost, and onemore » high explosive test, SPLAT, were conducted within the U12t Tunnel from 1970 to 1987. All six of the nuclear weapons effects tests and the high explosive test were sponsored by DTRA. Two conventional weapons experiments, Dipole Knight and Divine Eagle, were conducted in the tunnel portal area in 1997 and 1998. These experiments were sponsored by the Defense Special Weapons Agency. The U12t Tunnel complex is composed of the Portal and Mesa Areas and includes an underground tunnel with a main access drift and nine primary drifts, a substantial tailings pile fronting the tunnel portal, a series of discharge ponds downslope of the tailings pile, and two instrumentation trailer parks and 16 drill holes on top of Aqueduct Mesa. A total of 89 cultural features were recorded: 54 at the portal and 35 on the mesa. In the Portal Area, cultural features are mostly concrete pads and building foundations; other features include the portal, rail lines, the camel back, ventilation and cooling system components, communication equipment, and electrical equipment. On the mesa are drill holes, a few concrete pads, a loading ramp, and electrical equipment.« less

  17. High fusion performance at high T i/T e in JET-ILW baseline plasmas with high NBI heating power and low gas puffing

    NASA Astrophysics Data System (ADS)

    Kim, Hyun-Tae; Sips, A. C. C.; Romanelli, M.; Challis, C. D.; Rimini, F.; Garzotti, L.; Lerche, E.; Buchanan, J.; Yuan, X.; Kaye, S.; contributors, JET

    2018-03-01

    This paper presents the transport analysis of high density baseline discharges in the 2016 experimental campaign of the Joint European Torus with the ITER-Like Wall (JET-ILW), where a significant increase in the deuterium-deuterium (D-D) fusion neutron rate (~2.8  ×  1016 s-1) was achieved with stable high neutral beam injection (NBI) powers of up to 28 MW and low gas puffing. Increase in T i exceeding T e were produced for the first time in baseline discharges despite the high electron density; this enabled a significant increase in the thermal fusion reaction rate. As a result, the new achieved record in fusion performance was much higher than the previous record in the same heating power baseline discharges, where T i  =  T e. In addition to the decreases in collisionality and the increases in ion heating fraction in the discharges with high NBI power, T i  >  T e can also be attributed to positive feedback between the high T i/T e ratio and stabilisation of the turbulent heat flux resulting from the ion temperature gradient driven mode. The high T i/T e ratio was correlated with high rotation frequency. Among the discharges with identical beam heating power, higher rotation frequencies were observed when particle fuelling was provided by low gas puffing and pellet injection. This reveals that particle fuelling played a key role for achieving high T i/T e, and the improved fusion performance.

  18. High fusion performance at high T i/ T e in JET-ILW baseline plasmas with high NBI heating power and low gas puffing

    DOE PAGES

    Kim, Hyun-Tae; Sips, A. C. C.; Romanelli, M.; ...

    2018-02-01

    This article presents the transport analysis of high density baseline discharges in the 2016 experimental campaign of the Joint European Torus with the ITER-Like Wall (JET-ILW), where a significant increase in the deuterium–deuterium (D–D) fusion neutron rate (~2.8 × 10 16 s -1) was achieved with stable high neutral beam injection (NBI) powers of up to 28 MW and low gas puffing. Increase in T i exceeding T e were produced for the first time in baseline discharges despite the high electron density; this enabled a significant increase in the thermal fusion reaction rate. As a result, the new achievedmore » record in fusion performance was much higher than the previous record in the same heating power baseline discharges, where T i = T e. In addition to the decreases in collisionality and the increases in ion heating fraction in the discharges with high NBI power, T i > T e can also be attributed to positive feedback between the high T i/T e ratio and stabilisation of the turbulent heat flux resulting from the ion temperature gradient driven mode. The high T i/T e ratio was correlated with high rotation frequency. Among the discharges with identical beam heating power, higher rotation frequencies were observed when particle fuelling was provided by low gas puffing and pellet injection. Lastly, this reveals that particle fuelling played a key role for achieving high T i/T e, and the improved fusion performance.« less

  19. High fusion performance at high T i/ T e in JET-ILW baseline plasmas with high NBI heating power and low gas puffing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Hyun-Tae; Sips, A. C. C.; Romanelli, M.

    This article presents the transport analysis of high density baseline discharges in the 2016 experimental campaign of the Joint European Torus with the ITER-Like Wall (JET-ILW), where a significant increase in the deuterium–deuterium (D–D) fusion neutron rate (~2.8 × 10 16 s -1) was achieved with stable high neutral beam injection (NBI) powers of up to 28 MW and low gas puffing. Increase in T i exceeding T e were produced for the first time in baseline discharges despite the high electron density; this enabled a significant increase in the thermal fusion reaction rate. As a result, the new achievedmore » record in fusion performance was much higher than the previous record in the same heating power baseline discharges, where T i = T e. In addition to the decreases in collisionality and the increases in ion heating fraction in the discharges with high NBI power, T i > T e can also be attributed to positive feedback between the high T i/T e ratio and stabilisation of the turbulent heat flux resulting from the ion temperature gradient driven mode. The high T i/T e ratio was correlated with high rotation frequency. Among the discharges with identical beam heating power, higher rotation frequencies were observed when particle fuelling was provided by low gas puffing and pellet injection. Lastly, this reveals that particle fuelling played a key role for achieving high T i/T e, and the improved fusion performance.« less

  20. Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration

    PubMed Central

    Pencina, Karol M.; Coady, Jeffry A.; Beleva, Yusnie M.; Bhasin, Shalender; Basaria, Shehzad

    2015-01-01

    Objective: To determine dose-dependent effects of T administration on voice changes in women with low T levels. Methods: Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3, 6.25, 12.5, or 25 mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics. Results: Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P < .05); these changes in pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed. Conclusion: Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice. PMID:25875779

  1. Functional Voice Testing Detects Early Changes in Vocal Pitch in Women During Testosterone Administration.

    PubMed

    Huang, Grace; Pencina, Karol M; Coady, Jeffry A; Beleva, Yusnie M; Bhasin, Shalender; Basaria, Shehzad

    2015-06-01

    To determine dose-dependent effects of T administration on voice changes in women with low T levels. Seventy-one women who have undergone a hysterectomy with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3, 6.25, 12.5, or 25 mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Voice handicap was measured by self-report using a validated voice handicap index questionnaire at baseline and 24 weeks after intervention. Functional voice testing was performed using the Kay Elemetrics-Computer Speech Lab to determine voice frequency, volume, and harmonics. Forty-six women with evaluable voice data at baseline and after intervention were included in the analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 13, 83, 106, 122, and 250 ng/dL in the placebo, 3-, 6.25-, 12.5-, and 25-mg groups, respectively. Analyses of acoustic voice parameters revealed significant lowering of average pitch in the 12.5- and 25-mg dose groups compared to placebo (P < .05); these changes in pitch were significantly related to increases in T concentrations. No significant dose- or concentration-dependent changes in self-reported voice handicap index scores were observed. Testosterone administration in women with low T levels over 24 weeks was associated with dose- and concentration-dependent decreases in average pitch in the higher dose groups. These changes were seen despite the lack of self-reported changes in voice.

  2. Investigation of Regional Influence of Magic-Angle Effect on T2 in Human Articular Cartilage with Osteoarthritis at 3 T

    PubMed Central

    Wang, Ligong; Regatte, Ravinder R.

    2014-01-01

    Rationale and Objectives The objectives of this research study were to determine the magic-angle effect on different subregions of in vivo human femoral cartilage through the quantitative assessment of the effect of static magnetic field orientation (B0) on transverse (T2) relaxation time at 3.0 T. Materials and Methods Healthy volunteers (n = 5l; mean age, 36.4 years) and clinical patients (n = 5; mean age, 64 years) with early osteoarthritis (OA) were scanned at 3.0-T magnetic resonance using an 8-channel phased-array knee coil (transmit-receive). Results The T2 maps revealed significantly greater values in ventral than in dorsal regions. When the cartilage regions were oriented at 55° to B0 (magic angle), the longest T2 values were detected in comparison with the neighboring regions oriented 90° and 180° (0°) to B0. The subregions oriented 180° (0°) to B0 showed the lowest T2 values. Conclusions The differences in T2 values of different subregions suggest that magic-angle effect needs to be considered when interpreting cartilage abnormalities in OA patients. PMID:25481517

  3. Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats

    PubMed Central

    Oliveira, Karen M; Lavor, Mário Sérgio L; Silva, Carla Maria O; Fukushima, Fabíola B; Rosado, Isabel R; Silva, Juneo F; Martins, Bernardo C; Guimarães, Laís B; Gomez, Marcus Vinícius; Melo, Marília M; Melo, Eliane G

    2014-01-01

    Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements. PMID:25120731

  4. Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

    PubMed

    Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

    2017-11-01

    In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  5. Estradiol targets T cell signaling pathways in human systemic lupus.

    PubMed

    Walters, Emily; Rider, Virginia; Abdou, Nabih I; Greenwell, Cindy; Svojanovsky, Stan; Smith, Peter; Kimler, Bruce F

    2009-12-01

    The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.

  6. Critical assessment of precracked specimen configuration and experimental test variables for stress corrosion testing of 7075-T6 aluminum alloy plate

    NASA Technical Reports Server (NTRS)

    Domack, M. S.

    1985-01-01

    A research program was conducted to critically assess the effects of precracked specimen configuration, stress intensity solutions, compliance relationships and other experimental test variables for stress corrosion testing of 7075-T6 aluminum alloy plate. Modified compact and double beam wedge-loaded specimens were tested and analyzed to determine the threshold stress intensity factor and stress corrosion crack growth rate. Stress intensity solutions and experimentally determined compliance relationships were developed and compared with other solutions available in the literature. Crack growth data suggests that more effective crack length measurement techniques are necessary to better characterize stress corrosion crack growth. Final load determined by specimen reloading and by compliance did not correlate well, and was considered a major source of interlaboratory variability. Test duration must be determined systematically, accounting for crack length measurement resolution, time for crack arrest, and experimental interferences. This work was conducted as part of a round robin program sponsored by ASTM committees G1.06 and E24.04 to develop a standard test method for stress corrosion testing using precracked specimens.

  7. Single Particle Tracking reveals two distinct environments for CD4 receptors at the surface of living T lymphocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mascalchi, Patrice; Lamort, Anne Sophie; Salome, Laurence

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer We studied the diffusion of single CD4 receptors on living lymphocytes. Black-Right-Pointing-Pointer This study reveals that CD4 receptors have either a random or confined diffusion. Black-Right-Pointing-Pointer The dynamics of unconfined CD4 receptors was accelerated by a temperature raise. Black-Right-Pointing-Pointer The dynamics of confined CD4 receptors was unchanged by a temperature raise. Black-Right-Pointing-Pointer Our results suggest the existence of two different environments for CD4 receptors. -- Abstract: We investigated the lateral diffusion of the HIV receptor CD4 at the surface of T lymphocytes at 20 Degree-Sign C and 37 Degree-Sign C by Single Particle Tracking using Quantum Dots. Wemore » found that the receptors presented two major distinct behaviors that were not equally affected by temperature changes. About half of the receptors showed a random diffusion with a diffusion coefficient increasing upon raising the temperature. The other half of the receptors was permanently or transiently confined with unchanged dynamics on raising the temperature. These observations suggest that two distinct subpopulations of CD4 receptors with different environments are present at the surface of living T lymphocytes.« less

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

    NASA Technical Reports Server (NTRS)

    Xu, Kuan-Man

    2006-01-01

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

  9. Testing Delivery Platforms for New Anticancer tRNA-Based Drugs

    DTIC Science & Technology

    2011-03-01

    measurement of aminoacylated killer tRNA. Killer tRNA aminoacylated with lysine via a ribozyme is sufficiently stable in the culture media to enable...translational efficiency which helps the design of optimal killer tRNAs. - Determined that the flexi- ribozyme can be used to attach non-serine amino acids to...tRNAs using the flexi- ribozyme strategy. REPORTABLE OUTCOME - A dual GFP-mCherry reporter plasmid DNA useful to monitor delivery of tRNA in

  10. Expression of MCM-3 and MCM-7 in Primary Cutaneous T-cell Lymphomas.

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Reich, Adam; Grzegrzolka, Jedrzej; Maj, Joanna; Dziegiel, Piotr

    2015-11-01

    Primary cutaneous T-cell lymphomas is a group of rare non-Hodgkin lymphomas, originally affecting the skin. Increased proliferation activity is a hallmark of diverse tumors and the proliferation rate, measured by the expression of various markers has a predictive value regarding the malignancy course. The aim of the present study was to evaluate the prognostic value and the potential correlation between the expression of proliferation markers Ki-67, MCM-3 and MCM-7, and clinicopathological data for different types of primary cutaneous T-cell lymphomas. Immunohistochemical reactions were performed on paraffin blocks obtained from 90 patients with mycosis fungoides (MF) and 21 patients with other CTCL (oCTCL), in comparison to 19 patients with benign inflammatory dermatosis (lichen planus, eczema), serving as control. Statistically significant differences in the expression of Ki-67, MCM-3 and MCM-7 were observed between oCTCL vs. the control group (29% vs. 5%; 17% vs. 5%; 13% vs. 1.5%, respectively, ANOVA with Scheffé post-hoc test: p<0.01). In both, MF and oCTCL Ki-67 expression highly correlated with the expression of MCM-3 (r=0.83; p<0.001 and r=0.91; p<0.001, respectively) and MCM-7 (r=0.84; p<0.001 and r=0.87; p<0.01, respectively; Pearson correlation test). Similarly, a strong positive correlation was observed between MCM-3 and MCM-7 (r=0.81, p<0.001 and r=0.85, p<0.001). Regarding the MF group, Ki-67 and MCM-3 expression was significantly higher in advanced compared to early stages (11% vs. 3% and 15.5% vs. 5.0%, respectively, Student's t-test: p<0.05). Advanced MF had also significantly higher labeling indexes for Ki-67, MCM-3 and MCM-7 compared to benign inflammatory dermatoses (Student's t-test: p<0.01, p<0.001 and p=0.02, respectively). Considering skin involvement in MF, T1b had a significantly higher expression of Ki-67, MCM-3 and MCM-7 than T1a (p<0.001 for all comparisons) with similar observations between T2b and T2a (p=0.02; p<0.01; p=0

  11. “Don't let the world become too small” – How patients with advanced cancer and their significant others cope with transitions during the last year of life. A qualitative study

    PubMed

    Chabloz-Süssenbach, Christiane; Sailer Schramm, Monique; Stoll, Hansruedi; Spirig, Rebecca

    2016-07-01

    Background: In the last year of life, persons with advanced cancer and their significant others are affected by several transitions. They perform psychological adjustment processes during transformation. This requires strategies for patients and their significant others. Research in German about this theme is missing. Aim: We explored the experiences with illness management during transitions in the last year of life of patients with advanced cancer and their significant others. Method: In this qualitative study, we conducted structured interviews with five dyads, consisting of persons with Karnofsky Index ≥ 60 % and life expectancy of six to twelve months as well as their significant others. To interpret the interviews, we used qualitative content analysis according to Mayring. Results: The main theme “Don't let the world become too small” expresses that limitations diminished the lifeworld and the participants struggled against this process. This is revealed in three categories: “Being shocked by diagnosis – realigning again”, “Bearing limitations and loss – finding new ways in daily life”, “Living in uncertainty – holding out together”. Conclusions: Patients and significant others live in changing lifeworlds caused by transitions. Health care professionals should be attentive and may gain deeper knowledge about transitions. Further research in German-speaking contexts will help to improve nursing care and psychooncological interventions.

  12. Reliability and criterion-related validity of a new repeated agility test

    PubMed Central

    Makni, E; Jemni, M; Elloumi, M; Chamari, K; Nabli, MA; Padulo, J; Moalla, W

    2016-01-01

    The study aimed to assess the reliability and the criterion-related validity of a new repeated sprint T-test (RSTT) that includes intense multidirectional intermittent efforts. The RSTT consisted of 7 maximal repeated executions of the agility T-test with 25 s of passive recovery rest in between. Forty-five team sports players performed two RSTTs separated by 3 days to assess the reliability of best time (BT) and total time (TT) of the RSTT. The intra-class correlation coefficient analysis revealed a high relative reliability between test and retest for BT and TT (>0.90). The standard error of measurement (<0.50) showed that the RSTT has a good absolute reliability. The minimal detectable change values for BT and TT related to the RSTT were 0.09 s and 0.58 s, respectively. To check the criterion-related validity of the RSTT, players performed a repeated linear sprint (RLS) and a repeated sprint with changes of direction (RSCD). Significant correlations between the BT and TT of the RLS, RSCD and RSTT were observed (p<0.001). The RSTT is, therefore, a reliable and valid measure of the intermittent repeated sprint agility performance. As this ability is required in all team sports, it is suggested that team sports coaches, fitness coaches and sports scientists consider this test in their training follow-up. PMID:27274109

  13. Cost consequences of point-of-care troponin T testing in a Swedish primary health care setting

    PubMed Central

    Andersson, Agneta; Janzon, Magnus; Karlsson, Jan-Erik; Levin, Lars-Åke

    2014-01-01

    Abstract Objective. To evaluate the safety and cost-effectiveness of point-of-care troponin T testing (POCT-TnT) for the management of patients with chest pain in primary care. Design. Prospective observational study with follow-up. Setting. Three primary health care (PHC) centres using POCT-TnT and four PHC centres not using POCT-TnT in south-east Sweden. Patients. All patients ≥ 35 years of age, contacting one of the PHC centres for chest pain, dyspnoea on exertion, unexplained weakness and/or fatigue, with no other probable cause than cardiac, were included. Symptoms must have commenced or worsened during the previous seven days. Main outcome measures. Emergency referral rates, diagnoses of acute myocardial infarction (AMI) or unstable angina (UA), and costs were collected for 30 days after the patient sought care at the PHC centre. Results. A total of 196 patients with chest pain were included: 128 in PHC centres with POCT-TnT and 68 in PHC centres without POCT-TnT. Fewer patients from the PHC centres with POCT-TnT (n = 32, 25%) were emergently referred to hospital than from centres without POCT-TnT (n = 29, 43%; p = 0.011). Eight patients (6.2%) from PHC centres with POCT-TnT were diagnosed with AMI or UA compared with six patients (8.8%) from centres without POCT-TnT (p = 0.565). Two patients with AMI or UA were classified as missed cases from PHC centres with POCT-TnT and there were no missed cases from PHC centres without POCT-TnT. SKr290 000 was saved per missed case of AMI or UA. Conclusion. The use of POCT-TnT in primary care may be cost saving but at the expense of missed cases. PMID:25434410

  14. Reliability and validity of the 6-min walk test in adults and seniors with intellectual disabilities.

    PubMed

    Guerra-Balic, Myriam; Oviedo, Guillermo R; Javierre, Casimiro; Fortuño, Jesús; Barnet-López, Silvia; Niño, Oscar; Alamo, Juan; Fernhall, Bo

    2015-12-01

    Adults with intellectual disabilities (ID) have significantly lower rates of physical activity and fitness than adults without ID. The 6-min walk test (6 MWT) is an inexpensive and simple way to test mobility and submaximal work capacity. To evaluate the test-retest reliability and validity of the 6 MWT in adults and seniors with ID and explore factors contributing to the 6 MWT distance (6 MWD). 46 participants with mild, moderate and severe ID levels (age=41 ± 11 years) performed the 6 MWT three times (T1; T2; T3) to determine test-retest reliability. To test validity, peak oxygen uptake (VO2 peak) was measured using a treadmill protocol. To analyze factors contributing to the 6 MWD, sex, height, fat mass % and fat free mass %, ID level, isometric leg strength and relative VO2 peak were also measured. The walking distances for T1, T2 and T3 were 460.3 ± 76.9; 489.4 ± 81.2 and 491.4 ± 77.9 m, respectively. The 6 MWDs between T1-T2 and T1-T3 were significantly different (p<0.001), but T2 and T3 were not different. The intraclass correlation coefficient between T2 and T3 was 0.96 indicating high reliability. Relative VO2 peak and isometric leg strength significantly contributed to the 6 MWD (R(2)=0.55). The 6 MWT is an easy, inexpensive, reliable and valid test in adults and seniors with ID. Familiarization is necessary to obtain reliable values. Relative VO2 peak and leg strength have significant impact on the distance walked. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Metacognitive Ability Relationship with Test Result of Senior High School of Biology Teacher Competence in Sijunjung District

    NASA Astrophysics Data System (ADS)

    Ardi, A.; Fadilah, M.; Ichsani, W.

    2018-04-01

    This research aimed to reveal how the relationship between metacognitive ability and the test result of biology teacher competence in Sijunjung District. The population of this descriptive research were all high school biology teachers in Sijunjung District, and sample is all teachers who are members of the population, which is 23 biology teachers. The instrument used in this research are a questionnaire of research on teacher's metacognitive ability and document about teacher competence test result. The questionnaire was validated first by two lecturers of biology and one lecturer of English. Data analysis using Pearson Product Moment's. Based on the results of research and discussion that have been described, it can generally be concluded that there is a low relationship between metacognitive ability with competence test results of high school biology teachers in Sijunjung District. Partially, the relationship of metacognitive ability with the test result of professional competence of biology teacher showed significant result, with correlation coefficient 0,46 and t table 1,72 while titung 2,37. The contribution of metacognitive ability to the competence test result of the teacher is 21.6%, while the other 78.4% have not been revealed in this research.

  16. The t-CWT: a new ERP detection and quantification method based on the continuous wavelet transform and Student's t-statistics.

    PubMed

    Bostanov, Vladimir; Kotchoubey, Boris

    2006-12-01

    This study was aimed at developing a method for extraction and assessment of event-related brain potentials (ERP) from single-trials. This method should be applicable in the assessment of single persons' ERPs and should be able to handle both single ERP components and whole waveforms. We adopted a recently developed ERP feature extraction method, the t-CWT, for the purposes of hypothesis testing in the statistical assessment of ERPs. The t-CWT is based on the continuous wavelet transform (CWT) and Student's t-statistics. The method was tested in two ERP paradigms, oddball and semantic priming, by assessing individual-participant data on a single-trial basis, and testing the significance of selected ERP components, P300 and N400, as well as of whole ERP waveforms. The t-CWT was also compared to other univariate and multivariate ERP assessment methods: peak picking, area computation, discrete wavelet transform (DWT) and principal component analysis (PCA). The t-CWT produced better results than all of the other assessment methods it was compared with. The t-CWT can be used as a reliable and powerful method for ERP-component detection and testing of statistical hypotheses concerning both single ERP components and whole waveforms extracted from either single persons' or group data. The t-CWT is the first such method based explicitly on the criteria of maximal statistical difference between two average ERPs in the time-frequency domain and is particularly suitable for ERP assessment of individual data (e.g. in clinical settings), but also for the investigation of small and/or novel ERP effects from group data.

  17. Regional Contrasts of the Warming Rate over Land Significantly Depend on the Calculation Methods of Mean Air Temperature

    NASA Astrophysics Data System (ADS)

    Wang, Kaicun; Zhou, Chunlüe

    2016-04-01

    Global analyses of surface mean air temperature (Tm) are key datasets for climate change studies and provide fundamental evidences for global warming. However, the causes of regional contrasts in the warming rate revealed by such datasets, i.e., enhanced warming rates over the northern high latitudes and the "warming hole" over the central U.S., are still under debate. Here we show these regional contrasts depends on the calculation methods of Tm. Existing global analyses calculated Tm from daily minimum and maximum temperatures (T2). We found that T2 has a significant standard deviation error of 0.23 °C/decade in depicting the regional warming rate from 2000 to 2013 but can be reduced by two-thirds using Tm calculated from observations at four specific times (T4), which samples diurnal cycle of land surface air temperature more often. From 1973 to 1997, compared with T4, T2 significantly underestimated the warming rate over the central U.S. and overestimated the warming rate over the northern high latitudes. The ratio of the warming rate over China to that over the U.S. reduces from 2.3 by T2 to 1.4 by T4. This study shows that the studies of regional warming can be substantially improved by T4 instead of T2.

  18. Fabrication of 6FDA-durene membrane incorporated with zeolite T and aminosilane grafted zeolite T for CO2/CH4 separation

    NASA Astrophysics Data System (ADS)

    Jusoh, Norwahyu; Fong Yeong, Yin; Keong Lau, Kok; Shariff, Azmi Mohd

    2017-08-01

    In the present work, zeolite T and aminosilane grafted zeolite T are embedded into 6FDA-durene polyimide phase for the fabrication of mixed matrix membranes (MMMs). FESEM images demonstrated that the improvement of interfacial adhesion between zeolite and polymer phases in MMM loaded with aminosilane grafted zeolite T was not significant as compared to zeolite T/6FDA-durene MMM. From the gas permeation test, CO2/CH4 selectivity up to 26.4 was achieved using MMM containing aminosilane grafted zeolite T, while MMM loaded with ungrafted zeolite T showed CO2/CH4 selectivity of 19.1. In addition, MMM incorporated with aminosilane grafted zeolite T particles successfully lies on Robeson upper bound 2008, which makes it an attractive candidate for CO2/CH4 separation.

  19. Functional and quantitative alterations in T lymphocyte subpopulations in acute toxoplasmosis.

    PubMed

    Luft, B J; Kansas, G; Engleman, E G; Remington, J S

    1984-11-01

    The cellular immune response to Toxoplasma gondii has been studied in 23 patients with acute toxoplasma infection. Abnormalities of T cell subpopulations included a marked and significant elevation in suppressor (Leu 2) T cells in patients with prolonged symptoms due to acute infection and either a decrease in the number of T helper cells or an increase in the number of suppressor cells--or both--in patients with asymptomatic lymphadenopathy. There was no significant difference in lymphocyte proliferation to phytohemagglutinin or pokeweed mitogen among the various groups tested. The peak lymphocyte response to toxoplasma antigen, however, was significantly depressed in patients with acute infection compared with that in chronically infected control patients. The kinetics of the depression were consistent with the induction of a non-Leu 2 suppressor cell. These results demonstrate marked quantitative alterations in T lymphocyte subpopulations and functional alterations of T cells to toxoplasma antigen during infection with T. gondii.

  20. T-cell receptor gene rearrangement in Epstein-Barr virus infectious mononucleosis.

    PubMed

    Marbello, L; Riva, M; Veronese, S; Nosari, A M; Ravano, E; Colosimo, A; Paris, L; Morra, E

    2012-09-01

    This report describes the case of a previously healthy young man who presented with fever, pharyngitis, cervical lymphadenopathy, lymphocytosis, and severe thrombocytopenia. Serological tests for Epstein-Barr virus were diagnostic of a primary Epstein-Barr virus infectious mononucleosis but severe thrombocytopenia aroused the suspicion of a lymphoproliferative disease. T-cell receptor gene analysis performed on peripheral and bone marrow blood revealed a T-cell receptor γ-chain rearrangement without the evidence of malignancy using standard histologic and immunophenotype studies. Signs and symptoms of the infectious disease, blood count, and T-cell receptor gene rearrangement resolved with observation without the evidence of emergence of a lymphoproliferative disease. In the contest of a suspected lymphoproliferative disease, molecular results should be integrated with all available data for an appropriate diagnosis.