RESUMEN
Automatic tracking of viral structures displayed as small spots in fluorescence microscopy images is an important task to determine quantitative information about cellular processes. We introduce a novel probabilistic approach for tracking multiple particles based on multi-sensor data fusion and Bayesian smoothing methods. The approach exploits multiple measurements as in a particle filter, both detection-based measurements and prediction-based measurements from a Kalman filter using probabilistic data association with elliptical sampling. Compared to previous probabilistic tracking methods, our approach exploits separate uncertainties for the detection-based and prediction-based measurements, and integrates them by a sequential multi-sensor data fusion method. In addition, information from both past and future time points is taken into account by a Bayesian smoothing method in conjunction with the covariance intersection algorithm for data fusion. Also, motion information based on displacements is used to improve correspondence finding. Our approach has been evaluated on data of the Particle Tracking Challenge and yielded state-of-the-art results or outperformed previous approaches. We also applied our approach to challenging time-lapse fluorescence microscopy data of human immunodeficiency virus type 1 and hepatitis C virus proteins acquired with different types of microscopes and spatial-temporal resolutions. It turned out, that our approach outperforms existing methods.
Asunto(s)
Algoritmos , Estructuras Virales , Teorema de Bayes , Humanos , Microscopía FluorescenteRESUMEN
Cell segmentation in microscopy images is a common and challenging task. In recent years, deep neural networks achieved remarkable improvements in the field of computer vision. The dominant paradigm in segmentation is using convolutional neural networks, less common are recurrent neural networks. In this work, we propose a new deep learning method for cell segmentation, which integrates convolutional neural networks and gated recurrent neural networks over multiple image scales to exploit the strength of both types of networks. To increase the robustness of the training and improve segmentation, we introduce a novel focal loss function. We also present a distributed scheme for optimized training of the integrated neural network. We applied our proposed method to challenging data of glioblastoma cell nuclei and performed a quantitative comparison with state-of-the-art methods. Insights on how our extensions affect training and inference are also provided. Moreover, we benchmarked our method using a wide spectrum of all 22 real microscopy datasets of the Cell Tracking Challenge.
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Técnicas Citológicas/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Glioblastoma/patología , Humanos , Microscopía , Modelos EstadísticosRESUMEN
To investigate the neuropsychological profile in the first few years post-onset of relapsing-remitting multiple sclerosis (MS) we carried out a comprehensive neuropsychological evaluation of 33 patients characterized by very short evolution of this disease, minimal levels of neurological disability and preserved general cognition. Thirty-three individually pair-matched controls were also evaluated. Patients performed as well as controls on many of the cognitive exploration measures. Nevertheless, the group of patients evinced a general slowness that affected motor execution and cognitive processing. Memory functions were characterized by preservation of working memory, retrieval or storage of information and a deficit at the acquisition phase in (verbal and visual) supraspan tasks. In addition, significant correlations were observed between some measures of information processing speed and memory. These results highlight the importance of studying cognitive deficits not only in the different subtypes of MS but also in different phases of the disease.
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Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Adulto , Atención , Trastornos del Conocimiento/diagnóstico , Diagnóstico Precoz , Femenino , Humanos , Masculino , Memoria a Corto Plazo , Esclerosis Múltiple Recurrente-Remitente/psicología , Pruebas Neuropsicológicas , Aprendizaje Verbal , Percepción VisualRESUMEN
INTRODUCTION: The heredodegenerative ataxias are a heterogeneous group of disorders affecting especially the cerebellum and its tracts. Magnetic resonance imaging (MRI) studies using quantitative methodology are scarce, particularly in Friedreich's ataxia (FA). On the other hand, slowness of information processing speed has been described in FA, but no empirical relation with MRI parameters has been established. OBJECTIVE: The aim of the present study was to quantitatively assess infra and supratentorial atrophy in patients with clinical diagnosis of FA and to establish the relationship with a information processing speed measure. PATIENTS AND METHODS: Twelve FA patients that fulfilled clinical diagnostic criteria and twelve control subjects were studied. A computerized system that differentiate reaction time and movement time, as well as a semiautomated technique of binarization and analysis of MRI were used. RESULTS: Patients showed a poorer performance in movement time and in reaction time. Analyzing the frequency of pathologic changes, vermal atrophy was present in 67% of the patients and cerebellar hemisphere atrophy in 50%. Only a minority of patients showed signs of supratentorial cerebral atrophy (17%). Statistically significant negative correlations were obtained between reaction time and the size of the cerebellum. CONCLUSIONS: Cerebellar hemisphere atrophy is a usual finding in FA, although vermal atrophy is more frequent. The relation between cerebellar atrophy and reaction time supports the claim about cerebellar involvement in the information processing and response speed.
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Trastornos del Conocimiento/patología , Ataxia de Friedreich/patología , Imagen por Resonancia Magnética , Trastornos del Movimiento/patología , Tiempo de Reacción , Adulto , Atrofia/etiología , Atrofia/patología , Cerebelo/patología , Trastornos del Conocimiento/etiología , Femenino , Ataxia de Friedreich/complicaciones , Ataxia de Friedreich/fisiopatología , Ataxia de Friedreich/psicología , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/etiología , Pruebas Neuropsicológicas , Puente/patologíaRESUMEN
OBJECTIVE: Over the past 20 years great advances have been made in understanding the neuropsychological changes in multiple sclerosis. In this paper we review the nature of mental deterioration in multiple sclerosis and the procedures used for its evaluation. DEVELOPMENT: First we give a short summary of present knowledge of the involvement of different functions and the instruments most generally used to evaluate it. We then consider the different approaches to neuropsychological assessment, the use of broad guidelines as opposed to screening techniques, bearing in mind their advantages and disadvantages in the clinical field and in investigation. Similarly we mention the current trends in the evaluation and treatment of multiple sclerosis. CONCLUSIONS: The general profile of neuropsychological alterations in multiple sclerosis is characterized by the presence of changes in secondary memory and speed of thought, although the nature of this defect is still not clear. Changes are also seen in other neuropsychological functions, although less frequently and more controversially. Our knowledge of the prevalence of these changes comes from the use of guidelines for thorough examination. However, the current tendency is to seek instruments for evaluation which combine diagnostic efficiency, clinical usefulness and brevity. In this respect, although progress is being made, there are still questions to be answered.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Esclerosis Múltiple/complicaciones , Pruebas Neuropsicológicas , HumanosRESUMEN
An extracellular esterase from the actinomycetes Amycolatopsis orientalis was found by screening. It is capable of splitting the isomeric mixture (K/J) of (I, Scheme 1) into 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid, pivalic acid, and acetaldehyde with a high yield. The purified enzyme of 55.4 Kd by SDS-PAGE shows an N-terminal sequence of VRTCADLVRTYDLPGAVTH. The isoelectric point is 8.9 +/- 0.1. It can be immobilized with good yield to VA-Epoxy Biosynth. Besides the above-mentioned reaction, the esterase cleaves many other esters such as methyl-2-chloropropionic acid.
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Cefalosporinas/síntesis química , Esterasas/química , Esterasas/metabolismo , Ácidos Pentanoicos , Profármacos , Actinobacteria/enzimología , Secuencia de Aminoácidos , Cefalosporinas/metabolismo , Esterasas/aislamiento & purificación , Ésteres , Fermentación , Cinética , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Especificidad por SustratoRESUMEN
The aminothiazolyl-cephalosporin RU 29 246, the active metabolite of the prodrug-ester HR 916, is active against strains producing the widespread plasmid-encoded TEM-1, TEM-2 and SHV-1 beta-lactamases. Except for TEM-7 the activity of RU 29 246 against strains producing extended broad spectrum beta-lactamases (TEM-3, TEM-5, TEM-6, SHV-2, SHV-4, SHV-5, CMY-1, CTX-M), however, is low. Relative hydrolysis rates of RU 29 246 are comparable with those of cefpodoxime, the active metabolite of CS-807, and are extremely low for the TEM-1 and SHV-1 beta-lactamases. The compound demonstrates remarkable inhibitory activity against the chromosomal beta-lactamase of Enterobacter cloacae P99. In the presence of 1.7 microM this enzyme loses 50% of its activity. At concentrations of 0.43, 0.003 and 0.01 micrograms/ml the compound binds preferentially to the penicillin-binding protein (PBP) 3 of Escherichia coli K12, to the PBPs 2x and 3 of Streptococcus pneumoniae R6 and to PBP 1 of Staphylococcus aureus SG 511, respectively.