356 research outputs found

    Towards the re-verification of process tank calibrations

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    Re-verification is needed to ensure that the calibration (the relationship between measured level and measured volume) that is obtained during commissioning hasn’t changed over time. This can be achieved, in part, by metering in solution and correlating with marks identified a priori. Mark identification and correlation are discussed and possible error sources are outlined

    Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

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    PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p 10(-4) associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.Peer reviewe

    Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

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    BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

    Mitochondrial simple sequenze repeats and 12s – rRNA gene reveal two distinct lineages of Crocidura russula (Mammalia, Sorcidae)

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    A short segment (135 bp) of the control region and a partial sequence (394 bp) of the 12S-rRNA gene in the mitochondrial DNA of Crocidura russula were analyzed in order to test a previous hypothesis regarding the presence of a gene flow disruption in northern Africa. This breakpoint would have separated northeast-African C. russula populations from the European (plus the northwest-African) populations. The analysis was carried out on specimens from Tunisia (C. r. cf agilis), Sardinia (C. r. ichnusae), and Pantelleria (C. r. cossyrensis), and on C. r. russula from Spain and Belgium. Two C. russula lineages were identified; they both shared R2 tandem repeated motifs of the same length (12 bp), but not the same primary structure. These simple sequence repeats were present in 12–23 copies in the right domain of the control region. Within the northeast-African populations, a polymorphism of repeat variants, not yet found in Europe, was recorded. A neighbor-join tree, which was built by sequences of the conserved 12S-rRNA gene, separated the two sister groups; it permitted us to date a divergence time of 0.5Myr. Our data discriminated two different mitochondrial lineages in accordance with the previous morphological and karyological data. Ecoclimatic barriers formed during the Middle Pleistocene broke the range of ancestral species in the Eastern Algeria (Kabile Mountains), leading to two genetically separate and modern lineages. The northeast-African lineage can today be located in Tunisia, Pantelleria, and Sardinia. The northwest- African lineage (Morocco and West Algeria), reaching Spain by anthropogenic introduction, spread over north Europe in modern times. The Palaearctic C. russula species is monophyletic, but a taxonomical revision (ie, to provide a full species rank for the northeast taxa and to put in synonymy some insular taxa) is required

    Treatment of mastitis during lactation

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    Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials

    Population genomics reveals that within-fungus polymorphism is common and maintained in populations of the mycorrhizal fungus Rhizophagus irregularis.

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    Arbuscular mycorrhizal (AM) fungi are symbionts of most plants, increasing plant growth and diversity. The model AM fungus Rhizophagus irregularis (isolate DAOM 197198) exhibits low within-fungus polymorphism. In contrast, another study reported high within-fungus variability. Experiments with other R. irregularis isolates suggest that within-fungus genetic variation can affect the fungal phenotype and plant growth, highlighting the biological importance of such variation. We investigated whether there is evidence of differing levels of within-fungus polymorphism in an R. irregularis population. We genotyped 20 isolates using restriction site-associated DNA sequencing and developed novel approaches for characterizing polymorphism among haploid nuclei. All isolates exhibited higher within-isolate poly-allelic single-nucleotide polymorphism (SNP) densities than DAOM 197198 in repeated and non-repeated sites mapped to the reference genome. Poly-allelic SNPs were independently confirmed. Allele frequencies within isolates deviated from diploids or tetraploids, or that expected for a strict dikaryote. Phylogeny based on poly-allelic sites was robust and mirrored the standard phylogeny. This indicates that within-fungus genetic variation is maintained in AM fungal populations. Our results predict a heterokaryotic state in the population, considerable differences in copy number variation among isolates and divergence among the copies, or aneuploidy in some isolates. The variation may be a combination of all of these hypotheses. Within-isolate genetic variation in R. irregularis leads to large differences in plant growth. Therefore, characterizing genomic variation within AM fungal populations is of major ecological importance

    Measures and Limits of Models of Fixation Selection

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    Models of fixation selection are a central tool in the quest to understand how the human mind selects relevant information. Using this tool in the evaluation of competing claims often requires comparing different models' relative performance in predicting eye movements. However, studies use a wide variety of performance measures with markedly different properties, which makes a comparison difficult. We make three main contributions to this line of research: First we argue for a set of desirable properties, review commonly used measures, and conclude that no single measure unites all desirable properties. However the area under the ROC curve (a classification measure) and the KL-divergence (a distance measure of probability distributions) combine many desirable properties and allow a meaningful comparison of critical model performance. We give an analytical proof of the linearity of the ROC measure with respect to averaging over subjects and demonstrate an appropriate correction of entropy-based measures like KL-divergence for small sample sizes in the context of eye-tracking data. Second, we provide a lower bound and an upper bound of these measures, based on image-independent properties of fixation data and between subject consistency respectively. Based on these bounds it is possible to give a reference frame to judge the predictive power of a model of fixation selection . We provide open-source python code to compute the reference frame. Third, we show that the upper, between subject consistency bound holds only for models that predict averages of subject populations. Departing from this we show that incorporating subject-specific viewing behavior can generate predictions which surpass that upper bound. Taken together, these findings lay out the required information that allow a well-founded judgment of the quality of any model of fixation selection and should therefore be reported when a new model is introduced

    Functional Implication of Dp71 in Osmoregulation and Vascular Permeability of the Retina

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    Functional alterations of Müller cells, the principal glia of the retina, are an early hallmark of most retina diseases and contribute to their further progression. The molecular mechanisms of these reactive Müller cell alterations, resulting in disturbed retinal homeostasis, remain largely unknown. Here we show that experimental detachment of mouse retina induces mislocation of the inwardly rectifying potassium channels (Kir4.1) and a downregulation of the water channel protein (AQP4) in Müller cells. These alterations are associated with a strong decrease of Dp71, a cytoskeleton protein responsible for the localization and the clustering of Kir4.1 and AQP4. Partial (in detached retinas) or total depletion of Dp71 in Müller cells (in Dp71-null mice) impairs the capability of volume regulation of Müller cells under osmotic stress. The abnormal swelling of Müller cells In Dp71-null mice involves the action of inflammatory mediators. Moreover, we investigated whether the alterations in Müller cells of Dp71-null mice may interfere with their regulatory effect on the blood-retina barrier. In the absence of Dp71, the retinal vascular permeability was increased as compared to the controls. Our results reveal that Dp71 is crucially implicated in the maintenance of potassium homeostasis, in transmembraneous water transport, and in the Müller cell-mediated regulation of retinal vascular permeability. Furthermore, our data provide novel insights into the mechanisms of retinal homeostasis provided by Müller cells under normal and pathological conditions
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