Ultra high performance liquid chromatography with quadrupole/time-of-flight mass spectrometry was applied to evaluate the potential of nontarget metabolomic fingerprinting in order to distinguish Fusarium-infected and control barley samples. First, the sample extraction and instrumental conditions were optimized to obtain the broadest possible representation of polar/medium-polar compounds occurring in extracts obtained from barley grain samples. Next, metabolomic fingerprints of extracts obtained from nine barley varieties were acquired under ESI conditions in both positive and negative mode. Each variety of barley was tested in two variants: artificially infected by Fusarium culmorum at the beginning of heading and a control group (no infection). In addition, the dynamics of barley infection development was monitored using this approach. The experimental data were statistically evaluated by principal component analysis, hierarchical clustering analysis, and orthogonal partial least-squares discriminant analysis. The differentiation of barley in response to F. culmorum infection was feasible using this metabolomics-based method. Analysis in positive mode provided a higher number of molecular features as compared to that performed under negative mode setting. However, the analysis in negative mode permitted the detection of deoxynivalenol and deoxynivalenol-3-glucoside considered as resistance-indicator metabolites in barley.

• MeSH
• analýza hlavních komponent MeSH
• Fusarium fyziologie   MeSH
• hmotnostní spektrometrie MeSH
• ječmen (rod) metabolismus   mikrobiologie   MeSH
• metabolomika * MeSH
• metoda nejmenších čtverců MeSH
• nemoci rostlin mikrobiologie   MeSH
• shluková analýza MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Metalearning, an important part of artificial intelligence, represents a promising approach for the task of automatic selection of appropriate methods or algorithms. This paper is interested in recommending a suitable estimator for nonlinear regression modeling, particularly in recommending either the standard nonlinear least squares estimator or one of such available alternative estimators, which is highly robust with respect to the presence of outliers in the data. The authors hold the opinion that theoretical considerations will never be able to formulate such recommendations for the nonlinear regression context. Instead, metalearning is explored here as an original approach suitable for this task. In this paper, four different approaches for automatic method selection for nonlinear regression are proposed and computations over a training database of 643 real publicly available datasets are performed. Particularly, while the metalearning results may be harmed by the imbalanced number of groups, an effective approach yields much improved results, performing a novel combination of supervised feature selection by random forest and oversampling by synthetic minority oversampling technique (SMOTE). As a by-product, the computations bring arguments in favor of the very recent nonlinear least weighted squares estimator, which turns out to outperform other (and much more renowned) estimators in a quite large percentage of datasets.

• MeSH
• algoritmy * MeSH
• metoda nejmenších čtverců MeSH
• umělá inteligence * MeSH
• Publikační typ
• časopisecké články MeSH

Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R)-(+)-warfarin and (S)-(-)-warfarin. A new liquid chromatography method for the determination of both enantiomers was developed, validated and applied in in vitro studies with the aim of evaluating the accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line. OptiMEM cell cultivation medium samples and cellular lysates were purified using Waters Oasis MAX extraction cartridges. The chiral separation of warfarin and the internal standard p-chlorowarfarin enantiomers was performed on an Astec Chirobiotic V2 column at a flow rate of 1.2mL/min. The mobile phase was composed of 31% acetonitrile, 5% of methanol and 64% of ammonium acetate buffer (10mmol/L, pH 4.1). The enantiomers were quantified using a fluorescence detector (lambda(excit)=320nm, lambda(emiss)=415nm). The limit of detection was found to be 0.121micromol/L of (S)-warfarin and 0.109micromol/L of (R)-warfarin. The range of applicability and linearity was estimated from 0.25 to 100micromol/L. The precision ranged from 1.3% to 12.2% of the relative standard deviation, and the accuracy reached acceptable values from 95.5% to 108.4%. The new bioanalytical method confirmed the same accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line.

• MeSH
• fluorescence MeSH
• glykopeptidy chemie   MeSH
• lidé MeSH
• metoda nejmenších čtverců MeSH
• nádorové buněčné linie MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• warfarin analýza   chemie   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In contrast with numerous reports on the pharmacological effects of boldine, the data about its pharmacokinetics and biotransformation are scarce. No validated bioanalytical method of sufficient sensitivity has so far been described in the literature which could be used for quantification of boldine in various body fluids collected in pharmacokinetic studies. This work presents, for the first time, the assay for boldine in the plasma, bile and urine of rats. It includes liquid-liquid extraction/back-extraction of boldine, its chromatographic separation and sensitive fluorescence detection. Separation was carried out on a pentafluorophenyl core-shell column (Kinetex PFP, 150×3mm, 2.6μm) in gradient elution mode with solvent system consisting of an acetonitrile-ammonium formate buffer (5mM, pH=3.8). Fluorimetric detection (λEX=320nm, λEM=370nm) was used for quantitative work. Validation according to the EMEA guideline proved the assay LLOQ (0.1μmolL(-1)), linearity over a broad range of 0.1-50μmolL(-1), precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and accuracy (relative errors between -5.8% and 4.8%). In a pilot pharmacokinetic experiment, the concentration-time profiles were described for boldine (single i.v. bolus 50mgkg(-1)) in plasma and bile and cumulative excretion in urine was investigated. The major metabolites identified by means of LC-MS(n) were boldine-O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O-sulphate and N-demethyl-boldine-O-sulphate.

• MeSH
• aporfiny analýza   chemie   farmakokinetika   MeSH
• fluorescenční spektrometrie MeSH
• krysa rodu rattus MeSH
• metoda nejmenších čtverců MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• stabilita léku MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• žluč chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• matematika MeSH
• metoda nejmenších čtverců MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Kombinatorika. Teorie grafů. Matematická statistika. Operační výzkum. Matematické modelování
• NLK Obory
• statistika, zdravotnická statistika

OBJECTIVES: The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. METHODS: Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. RESULTS: Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). CONCLUSIONS: In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.

• MeSH
• 5'-nukleotidasa imunologie   MeSH
• autoimunitní nemoci imunologie   MeSH
• autoprotilátky imunologie   MeSH
• dermatomyozitida diagnóza   imunologie   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida s inkluzními tělísky diagnóza   imunologie   MeSH
• neuromuskulární nemoci imunologie   MeSH
• polymyozitida diagnóza   imunologie   MeSH
• revmatoidní artritida imunologie   MeSH
• ROC křivka MeSH
• roztroušená skleróza imunologie   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Sjögrenův syndrom imunologie   MeSH
• studie případů a kontrol MeSH
• systémová sklerodermie imunologie   MeSH
• systémový lupus erythematodes imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

In this chapter, we demonstrate the advantage of the simultaneous multicurve nonlinear least-squares analysis over that of the conventional single-curve analysis. Fitting results are subjected to thorough Monte Carlo analysis for rigorous assessment of confidence intervals and parameter correlations. The comparison is performed on a practical example of simulated steady-state reaction kinetics complemented with isothermal calorimetry (ITC) data resembling allosteric behavior of rabbit muscle pyruvate kinase (RMPK). Global analysis improves accuracy and confidence limits of model parameters. Cross-correlation between parameters is also reduced with accompanying enhancement of the model-testing power. This becomes especially important for validation of models with "difficult" highly cross-correlated parameters. We show how proper experimental design and critical evaluation of data can improve the chance of differentiating models.

• MeSH
• kalorimetrie MeSH
• králíci MeSH
• metoda Monte Carlo MeSH
• metoda nejmenších čtverců MeSH
• pyruvátkinasa chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Quantification models based on the processing of FTIR spectra by partial least squares regression (PLS) were created in order to develop a method for the determination of 2-ethylhexyl nitrate (2-EHN) in diesel fuels. The set of standards was prepared using 2-EHN, biodiesel (FAME) and various mineral diesel fuels (2-EHN free). The standards were prepared in the concentration range of 2-EHN of 0-2436mgkg-1. The set of the standards was divided into the calibration, validation and test sets. While the calibration set was used to build the model, validation set was used in order to optimize the model parameters. The test set of the standards was used to assess the predictive ability and repeatability of the model. Several hundreds of various models were developed and compared in order to find a suitable combination of the preprocessing methods and number of latent variables. The most promising model was developed using mean centered spectra in the form of their first derivative and smoothed using Gap-Segment derivative. The model showed quite good predictive ability and repeatability.

• MeSH
• benzin analýza   MeSH
• biopaliva analýza   MeSH
• dusičnany analýza   MeSH
• informatika * MeSH
• metoda nejmenších čtverců MeSH
• spektroskopie infračervená s Fourierovou transformací * MeSH
• Publikační typ
• časopisecké články MeSH

Visible near-infrared (Vis-NIR) reflection spectroscopy and mid-infrared (mid-IR) reflection spectroscopy are cost- and time-effective and environmentally friendly techniques that could be alternatives to conventional soil analysis methods. Successful determination of spectrally active soil components, including soil organic matter (SOM), depends on the selection of suitable pretreatment and multivariate calibration techniques. The objective of the present review is to critically examine the suitability of Vis-NIR (350-2500 nm) and mid-IR (4000-400 cm(-1)) spectroscopy as a tool for SOM quantity and quality determination. Particular attention is paid to different pretreatment and calibration procedures and methods, and their ability to predict SOM content from Vis-NIR and mid-IR data is discussed. We then review the most recent research using spectroscopy in different calibration scales (local, regional, or global). Finally, accuracy and robustness, as well as uncertainty in Vis-NIR and mid-IR spectroscopy, are considered. We conclude that spectroscopy, especially the mid-IR technique in association with Savitzky-Golay smoothing and derivatization and the least squares support vector machine (LS-SVM) algorithm, can be useful in determining SOM quantity and quality. Future research conducted for the standardization of protocols and soil conditions will allow more accurate and reliable results on a global and international scale.

• MeSH
• blízká infračervená spektroskopie metody   normy   MeSH
• kalibrace MeSH
• metoda nejmenších čtverců MeSH
• půda chemie   MeSH
• spektrofotometrie infračervená metody   normy   MeSH
• support vector machine MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Importance: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression. Objective: To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value. Design, Setting, and Participants: Phase 2, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 7 countries of eligible patients with IPF (N = 117; aged 40-80 years; FVC ≥50% and ≤90% predicted; ratio of forced expiratory volume in the first second/FVC >0.70; diffusing capacity for carbon monoxide [Dlco] ≥25% and ≤90% predicted; and distance of ≥150 m on the 6-minute walk test). Study period was August 2015-May 2017. Interventions: Patients were randomized to receive either recombinant human pentraxin 2 (10 mg/kg intravenous every 4 weeks, n = 77) or placebo (n = 39) for 24 weeks, and stratified by concurrent IPF treatment status. Main Outcomes and Measures: The primary end point was the least-squares mean change in FVC percentage of predicted value from baseline to week 28 (minimal clinically important difference, decline of 2%-6%). Secondary end points included mean change in lung volumes (total, normal, and interstitial lung abnormalities) on high-resolution computed tomography (HRCT) and 6-minute walk distance (minimal clinically important difference, 24-45 m). Results: Of 117 randomized patients, 116 received at least 1 dose of study drug (mean age, 68.6 years; 81.0% men; mean time since IPF diagnosis, 3.8 years), and 111 (95.7%) completed the study. The least-squares mean change in FVC percentage of predicted value from baseline to week 28 in patients treated with recombinant human pentraxin 2 was -2.5 vs -4.8 for those in the placebo group (difference, +2.3 [90% CI, 1.1 to 3.5]; P = .001). No significant treatment differences were observed in total lung volume (difference, 93.5 mL [90% CI, -27.7 to 214.7]), quantitative parenchymal features on HRCT (normal lung volume difference, -1.2% [90% CI, -4.4 to 1.9]; interstitial lung abnormalities difference, 1.1% [90% CI, -2.2 to 4.3]), or measurement of Dlco (difference, -0.4 [90% CI, -2.6 to 1.7]). The change in 6-minute walk distance was -0.5 m for patients treated with recombinant human pentraxin 2 vs -31.8 m for those in the placebo group (difference, +31.3 m [90% CI, 17.4 to 45.1]; P < .001). The most common adverse events in the recombinant human pentraxin 2 vs placebo group were cough (18% vs 5%), fatigue (17% vs 10%), and nasopharyngitis (16% vs 23%). Conclusions and Relevance: In this preliminary study, recombinant human pentraxin 2 vs placebo resulted in a slower decline in lung function over 28 weeks for patients with idiopathic pulmonary fibrosis. Further research should more fully assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT02550873.

• MeSH
• dvojitá slepá metoda MeSH
• homeodoménové proteiny škodlivé účinky   farmakologie   terapeutické užití   MeSH
• idiopatická plicní fibróza farmakoterapie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda nejmenších čtverců MeSH
• rekombinantní proteiny škodlivé účinky   farmakologie   terapeutické užití   MeSH
• senioři MeSH
• sérový amyloidový protein škodlivé účinky   farmakologie   terapeutické užití   MeSH
• test chůzí MeSH
• vitální kapacita účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH