Evaluation of steroidomics by liquid chromatography hyphenated to mass spectrometry as a powerful analytical strategy for measuring human steroid perturbations.

This review presents the evolution of steroid analytical techniques, including gas chromatography coupled to mass spectrometry (GC-MS), immunoassay (IA) and targeted liquid chromatography coupled to mass spectrometry (LC-MS), and it evaluates the potential of extended steroid profiles by a metabolomics-based approach, namely steroidomics. Steroids regulate essential biological functions including growth and reproduction, and perturbations of the steroid homeostasis can generate serious physiological issues; therefore, specific and sensitive methods have been developed to measure steroid concentrations. GC-MS measuring several steroids simultaneously was considered the first historical standard method for analysis. Steroids were then quantified by immunoassay, allowing a higher throughput; however, major drawbacks included the measurement of a single compound instead of a panel and cross-reactivity reactions. Targeted LC-MS methods with selected reaction monitoring (SRM) were then introduced for quantifying a small steroid subset without the problems of cross-reactivity. The next step was the integration of metabolomic approaches in the context of steroid analyses. As metabolomics tends to identify and quantify all the metabolites (i.e., the metabolome) in a specific system, appropriate strategies were proposed for discovering new biomarkers. Steroidomics, defined as the untargeted analysis of the steroid content in a sample, was implemented in several fields, including doping analysis, clinical studies, in vivo or in vitro toxicology assays, and more. This review discusses the current analytical methods for assessing steroid changes and compares them to steroidomics. Steroids, their pathways, their implications in diseases and the biological matrices in which they are analysed will first be described. Then, the different analytical strategies will be presented with a focus on their ability to obtain relevant information on the steroid pattern. The future technical requirements for improving steroid analysis will also be presented.

Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital, urban wastewater and river water by ultra-highperformance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry

The present work describes the development of a fast and robust analytical method for the determination of 53 antibiotic residues, covering various chemical groups and some of their metabolites, in environmental matrices that are considered important sources of antibiotic pollution, namely hospital and urban wastewaters, as well as in river waters. The method is based on automated off-line solid phase extraction (SPE) followed by ultra-high-performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry (UHPLC–QqLIT). For unequivocal identification and confirmation, and in order to fulfill EU guidelines, two selected reaction monitoring (SRM) transitions per compound are monitored (the most intense one is used for quantification and the second one for confirmation). Quantification of target antibiotics is performed by the internal standard approach, using one isotopically labeled compound for each chemical group, in order to correct matrix effects. The main advantages of the method are automation and speed-up of sample preparation, by the reduction of extraction volumes for all matrices, the fast separation of a wide spectrum of antibiotics by using ultra-high-performance liquid chromatography, its sensitivity (limits of detection in the low ng/L range) and selectivity (due to the use of tandem mass spectrometry) The inclusion of β-lactam antibiotics (penicillins and cephalosporins), which are compounds difficult to analyze in multi-residue methods due to their instability in water matrices, and some antibiotics metabolites are other important benefits of the method developed. As part of the validation procedure, the method developed was applied to the analysis of antibiotics residues in hospital, urban influent and effluent wastewaters as well as in river water samples

Simulation-based evaluation of susceptibility distortion correction methods in diffusion MRI for connectivity analysis

Connectivity analysis on diffusion MRI data of the whole- brain suffers from distortions caused by the standard echo- planar imaging acquisition strategies. These images show characteristic geometrical deformations and signal destruction that are an important drawback limiting the success of tractography algorithms. Several retrospective correction techniques are readily available. In this work, we use a digital phantom designed for the evaluation of connectivity pipelines. We subject the phantom to a âeurooetheoretically correctâeuro and plausible deformation that resembles the artifact under investigation. We correct data back, with three standard methodologies (namely fieldmap-based, reversed encoding-based, and registration- based). Finally, we rank the methods based on their geometrical accuracy, the dropout compensation, and their impact on the resulting connectivity matrices.

A comprehensive model for quantum noise characterization in digital mammography.

NlmCategory="UNASSIGNED">A version of cascaded systems analysis was developed specifically with the aim of studying quantum noise propagation in x-ray detectors. Signal and quantum noise propagation was then modelled in four types of x-ray detectors used for digital mammography: four flat panel systems, one computed radiography and one slot-scan silicon wafer based photon counting device. As required inputs to the model, the two dimensional (2D) modulation transfer function (MTF), noise power spectra (NPS) and detective quantum efficiency (DQE) were measured for six mammography systems that utilized these different detectors. A new method to reconstruct anisotropic 2D presampling MTF matrices from 1D radial MTFs measured along different angular directions across the detector is described; an image of a sharp, circular disc was used for this purpose. The effective pixel fill factor for the FP systems was determined from the axial 1D presampling MTFs measured with a square sharp edge along the two orthogonal directions of the pixel lattice. Expectation MTFs were then calculated by averaging the radial MTFs over all possible phases and the 2D EMTF formed with the same reconstruction technique used for the 2D presampling MTF. The quantum NPS was then established by noise decomposition from homogenous images acquired as a function of detector air kerma. This was further decomposed into the correlated and uncorrelated quantum components by fitting the radially averaged quantum NPS with the radially averaged EMTF(2). This whole procedure allowed a detailed analysis of the influence of aliasing, signal and noise decorrelation, x-ray capture efficiency and global secondary gain on NPS and detector DQE. The influence of noise statistics, pixel fill factor and additional electronic and fixed pattern noises on the DQE was also studied. The 2D cascaded model and decompositions performed on the acquired images also enlightened the observed quantum NPS and DQE anisotropy.

Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging.

Focal epilepsy is increasingly recognized as the result of an altered brain network, both on the structural and functional levels and the characterization of these widespread brain alterations is crucial for our understanding of the clinical manifestation of seizure and cognitive deficits as well as for the management of candidates to epilepsy surgery. Tractography based on Diffusion Tensor Imaging allows non-invasive mapping of white matter tracts in vivo. Recently, diffusion spectrum imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fiber crossing and recent developments allow acquisition times compatible with clinical application. We used DSI and parcellation of the gray matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical and subcortical regions in patients with focal epilepsy and healthy controls. In addition, the high angular and radial resolution of DSI allowed us to evaluate also some of the biophysical compartment models, to better understand the cause of the changes in diffusion anisotropy. Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

Systematic evaluation of matrix effects in hydrophilic interaction chromatography versus reversed phase liquid chromatography coupled to mass spectrometry.

Reversed phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) is the gold standard technique in bioanalysis. However, hydrophilic interaction chromatography (HILIC) could represent a viable alternative to RPLC for the analysis of polar and/or ionizable compounds, as it often provides higher MS sensitivity and alternative selectivity. Nevertheless, this technique can be also prone to matrix effects (ME). ME are one of the major issues in quantitative LC-MS bioanalysis. To ensure acceptable method performance (i.e., trueness and precision), a careful evaluation and minimization of ME is required. In the present study, the incidence of ME in HILIC-MS/MS and RPLC-MS/MS was compared for plasma and urine samples using two representative sets of 38 pharmaceutical compounds and 40 doping agents, respectively. The optimal generic chromatographic conditions in terms of selectivity with respect to interfering compounds were established in both chromatographic modes by testing three different stationary phases in each mode with different mobile phase pH. A second step involved the assessment of ME in RPLC and HILIC under the best generic conditions, using the post-extraction addition method. Biological samples were prepared using two different sample pre-treatments, i.e., a non-selective sample clean-up procedure (protein precipitation and simple dilution for plasma and urine samples, respectively) and a selective sample preparation, i.e., solid phase extraction for both matrices. The non-selective pretreatments led to significantly less ME in RPLC vs. HILIC conditions regardless of the matrix. On the contrary, HILIC appeared as a valuable alternative to RPLC for plasma and urine samples treated by a selective sample preparation. Indeed, in the case of selective sample preparation, the compounds influenced by ME were different in HILIC and RPLC, and lower and similar ME occurrence was generally observed in RPLC vs. HILIC for urine and plasma samples, respectively. The complementary of both chromatographic modes was also demonstrated, as ME was observed only scarcely for urine and plasma samples when selecting the most appropriate chromatographic mode.

A Write-Based Solver for SAT Modulo the Theory of Arrays

The extensional theory of arrays is one of the most important ones for applications of SAT Modulo Theories (SMT) to hardware and software verification. Here we present a new T-solver for arrays in the context of the DPLL(T) approach to SMT. The main characteristics of our solver are: (i) no translation of writes into reads is needed, (ii) there is no axiom instantiation, and (iii) the T-solver interacts with the Boolean engine by asking to split on equality literals between indices. As far as we know, this is the first accurate description of an array solver integrated in a state-of-the-art SMT solver and, unlike most state-of-the-art solvers, it is not based on a lazy instantiation of the array axioms. Moreover, it is very competitive in practice, specially on problems that require heavy reasoning on array literals

Caracterización morfológica del M2 de Primates Hominoidea a partir de análisis de Fourier

Los análisis de Fourier permiten caracterizar el contorno del diente a partir de un número determinado de puntos y extraer una serie de parámetros para un posterior análisis multivariante. No obstante, la gran complejidad que presentan algunas conformaciones, obliga a comprobar cuántos puntos son necesarios para una correcta representación de ésta. El objetivo de este trabajo es aplicar y validar los análisis de Fourier (Polar y Elíptico) en el estudio de la forma dental a partir de diferentes puntos de contorno y explorar la variabilidad morfométrica en diferentes géneros. Se obtuvieron fotografías digitales de la superfi cie oclusal en segundos molares inferiores (M2s) de 4 especies de Primates (Hylobates moloch, Gorilla beringei graueri, Pongo pygmaeus pygmaeus y Pan troglodytes schweirfurthii) y se defi nió su contorno con 30, 40, 60, 80, 100 y 120 puntos y su representación formal a 10 armónicos. El análisis de la variabilidad morfométrica se realizó mediante la aplicación de Análisis Discriminantes y un NP-MANOVA a partir de matrices de distancias para determinar la variabilidad y porcentajes de clasifi cacióncorrecta, a nivel metodológico y taxonómico. Los resultados indicaron que los análisis de forma con series de Fourier permiten analizar la variabilidad morfométrica de M2s en géneros de Hominoidea, con independencia del número de puntos de contorno (30 a 120). Los porcentajes de clasifi cación son más variables e inferiores con el uso de la serie Polar (≈60-90) que con la Elíptica (75-100%). Un número entre 60-100 puntos de contorno mediante el método elíptico garantiza una descripción correcta de la forma del diente.

Determinação simultânea de ânions por eletroforese capilar: características e aplicações

Capillary electrophoresis (CE) encompasses a number of characteristics quite suitable for the simultaneous analysis of small ions such as high efficiency and resolving power, directly associated to its impressively high peak capacity, and short analysis time. In appropriate conditions, it is possible to perform the separation of approximately 36 anions in less than 3 minutes. In this work, the mechanisms by which anion analysis is performed was criteriously discussed, and a thorough review of the literature in the past 5 years, focusing mostly in applications of CE to anion analysis in real matrices, was presented.

A contaminação dos oceanos por radionuclídeos antropogênicos

Several hundreds of artificial radionuclides are produced as the result of human activities, such as the applications of nuclear reactors and particle accelerators, testing of nuclear weapons and nuclear accidents. Many of these radionuclides are short-lived and decay quickly after their production, but some of them are longer-lived and are released into the environment. From the radiological point of view the most important radionuclides are cesium-137, strontium-90 and plutonium-239, due to their chemical and nuclear characteristics. The two first radioisotopes present long half life (30 and 28 years), high fission yields and chemical behaviour similar to potassium and calcium, respectively. No stable element exists for plutonium-239, that presents high radiotoxicity, long half-life (24000 years) and some marine organisms accumulate plutonium at high levels. The radionuclides introduced into marine environment undergo various physical, chemical and biological processes taking place in the sea. These processes may be due to physical dispersion or complicated chemical and biological interactions of the radionuclides with inorganic and organic suspend matter, variety of living organisms, bottom sediments, etc. The behaviour of radionuclides in the sea depends primarily on their chemical properties, but it may also be influenced by properties of interacting matrices and other environmental factors. The major route of radiation exposure of man to artificial radionuclides occuring in the marine environment is through ingestion of radiologically contamined marine organisms. This paper summarizes the main sources of contamination in the marine environment and presents an overview covering the oceanic distribution of anthropogenic radionuclides in the FAO regions. A great number of measurements of artificial radionuclides have been carried out on various marine environmental samples in different oceans over the world, being cesium-137 the most widely measured radionuclide. Radionuclide concentrations vary from region to region, according to the specific sources of contamination. In some regions, such as the Irish Sea, the Baltic Sea and the Black Sea, the concentrations depend on the inputs due to discharges from reprocessing facilities and from Chernobyl accident. In Brazil, the artificial radioactivity is low and corresponds to typical deposition values due to fallout for the Southern Hemisphere.

Hidrólise seletiva de carboxiamidas de resíduos de asparagina e glutamina em colágeno: preparação e caracterização de matrizes aniônicas para uso como biomateriais

This work describes the selective hydrolysis of carboxyamide groups of asparagine and glutamine of collagen matrices for the preparation of negatively charged collagen biomaterials. The reaction was performed in the presence of chloride and sulfate salts of alkaline and alkaline earth metals in aqueous dimethylsulfoxide solution and, selectively hydrolysis of carboxyamide groups of collagen matrices was promoted without cleavage of the peptide bond. The result is a new collagen material with controlled increase in negative charge content. Although triple helix secondary structure of tropocollagen was preserved, significative changes in thermal stabilities were observed in association with a new pattern of tropocollagen macromolecular association, particularly in respect microfibril assembly, thus providing at physiological pH a new type of collagen structure for biomaterial preparation, characterized by different charge and structural contents .

Classification of textures seen from different distances and under varying illumination direction

Changes in the angle of illumination incident upon a 3D surface texture can significantly alter its appearance, implying variations in the image texture. These texture variations produce displacements of class members in the feature space, increasing the failure rates of texture classifiers. To avoid this problem, a model-based texture recognition system which classifies textures seen from different distances and under different illumination directions is presented in this paper. The system works on the basis of a surface model obtained by means of 4-source colour photometric stereo, used to generate 2D image textures under different illumination directions. The recognition system combines coocurrence matrices for feature extraction with a Nearest Neighbour classifier. Moreover, the recognition allows one to guess the approximate direction of the illumination used to capture the test image

Alguns aspectos de imunoensaios aplicados à química analítica

In the last years, the use of antibody-antigen interactions, has earned attention not only for clinical analysis, but also for food industry and environmental control. Since the scope and diversity of immunoassay technology have shown a wide development. Continuous advances in order to analyse complex matrices, to improve reliability, simplicity (nonseparation) and to get multiple simultaneous assays, and extreme sensitivity (lower than zeptomole detection limits) are increasing. Many strategies have been investigated including chemiluminescent enzyme immunoassays, DNA as label and development of flow injection and immunosensors techniques. This subject became very usefull and important in nowadays that are taught in the undergraduate courses of chemistry in the european universities. However in our country are still ignored in the chemistry course.

Especiação de Arsênio - uma revisão

This paper provides a review on separation methods and analytical techniques for the determination of several species of organic and inorganic arsenic in different matrices. Arsenic is an element whose speciation is of particular interest due to the great variation of toxicity levels exhibited for its different chemical forms. Arsenic (III) and As (V) are the most toxic species while organic compounds such as arsenobetaine (AsB), produced by methylation of inorganics species (carcinogenics) are relatively less toxic, hence the great importance of arsenic speciation in the determination of the degree of contamination of an environmental or biological system.

Síntese de polímeros condutores em matrizes sólidas hospedeiras

This review discusses the methods used to prepare conductive polymers in confined environments. This spatial restriction causes formation of defect-free polymer chains in the interlayer as porous cavities of inorganic hosts. The properties of the different composites obtained are a synergist combination of the characteristics of the inorganic host and the polymer. This opens new perspectives for the preparation of these materials and widens its potential applications.