Добірка наукової літератури з теми "Surface fibrillation"

Pulp refining produces external fibrillation consisting of fibrils tethered to fiber surfaces, in addition to loose fibrils and fines. Both contribute to a larger bonding area that increases paper strength, but tethered fibrils have less likelihood of being washed out during papermaking. This study postulates the mechanism by which refining produces external fibrillation and the optimum conditions for doing so. The postulated mechanism is surface abrasion during sliding of fibers in refiner gaps. External fibrillation occurs when forces are great enough to partially dislodge fibrils from fiber surfaces, but not large enough to break the fibrils. The refining intensities to achieve these forces were determined by a mathematical model and experiments using a laboratory disc refiner. The optimum intensities in terms of specific edge load (SEL) for chemical pulps were about 0.1 J/m for hardwoods and 1.0 J/m for softwoods An extension of this study suggested that abrasion may also account for most of the energy consumed in the mechanical pulping process.

Solid surfaces have been shown to affect the aggregation and assembly of many biomolecular systems. One important example is the formation of protein fibrils, which can occur on a range of biological and synthetic surfaces. The rate of fibrillation depends on both the protein structure and the surface chemistry, with the different molecular and oligomer structures adopted by proteins on surfaces likely to be crucial. In this paper, the aggregation of the model amyloidogenic peptide, Aβ(16–22), corresponding to a hydrophobic segment of the amyloid beta protein on a gold surface is studied using molecular dynamics simulation. Previous simulations of this peptide on gold surfaces have shown that it adopts conformations on surfaces that are quite different from those in bulk solution. These simulations show that this then leads to significant differences in the oligomer structures formed in solution and on gold surfaces. In particular, oligomers formed on the surface are low in beta-strands so are unlike the structures formed in bulk solution. When oligomers formed in solution adsorb onto gold surfaces they can then restructure themselves. This can then help explain the inhibition of Aβ(16–22) fibrillation by gold surfaces and nanoparticles seen experimentally.

The longitudinal surfaces of Eucalyptus maculata wood sampies fractured either artificially (splitting) or naturally (drying stresses) at a range of moisture contents, were examined under a scanning eleetron microscope. In those sam pies above fibre saturation point, a relativeIy clean surface was produced, since the cells either separated in the outer regions of the wall with minimal fibrillation (fibres, some ray parenchyma), or the fracture path travelled abruptly through the wall exposing the lumen (vertical parenchyma, vessels, so me ray cells). Below fibre saturation, particularly as the air dry condition was approached, a fibrous, splintery surface resulted, due mainly to fibrillation and delamination of the secondary walls in fibres and ray parenchyma.

Atrial fibrillation (AF) is the most common rhythm disorder, and is strongly associated with thromboembolic events and heart failure. Over the past decade, catheter ablation of AF has advanced considerably with progressive improvement in success rates. However, interventional treatment is still challenging, especially for persistent and long-standing persistent AF. Recently, AF analysis using a non-invasive body surface mapping technique has been shown to identify localised reentrant and focal sources, which play an important role in driving and perpetuating AF. Non-invasive mapping-guided ablation has also been reported to be effective for persistent AF. In this review, we describe new clinical insights obtained from non-invasive mapping of persistent AF to guide catheter ablation.

A new surface modification method fibrillation combined with oxygen plasma treatment to improve the wettability and hydrophily of PBO fiber was studied in this paper. The surface chemical structure and morphology of PBO fiber were characterized by the methods of FTIR, XPS and SEM. The wettability and hydrophlic characters changes on the surface were evaluated by the dynamic contact angle system and image analysis. The results show that the increase surface roughness by fibrillation could improve the wettability. Fibrillation combined oxygen plasma treatment has a better effect than oxygen plasma treatment to improve the wettability and hdyrophlization of PBO fiber. The specific area of PBO fiber increased to 10.7 m2/g from 0.7 m2/g, contact angle decreased to 43.2° from 84.4° and WRV increased to 208.4% from 13.7%. The modified fibers have a good dispersion in water for hydrophilization improvement.

A 62 year old man was admitted for evaluation of recurrent episodes of syncope. A surface ECG showed frequent repetitive premature ventricular complexes of right ventricular outflow tract origin. Ventricular fibrillation was inducible by programmed electrical stimulation but otherwise cardiac evaluation was unremarkable. A diagnosis of idiopathic ventricular fibrillation was made and an implantable cardioverter-defibrillator (ICD) was installed. However, spontaneous ventricular fibrillation recurred, requiring repeated ICD discharges. The ventricular fibrillation was reproducibly triggered by a single premature ventricular complex with a specific QRS morphology. Radiofrequency catheter ablation was carried out to eradicate this complex. No ventricular fibrillation has developed after this procedure, and the patient does not require drug treatment.

La fibrilación auricular (FA) es una de las arritmias cardiacas más comunes, afectando a alrededor del 10 % de los mayores de 70 años. A pesar de su alta incidencia en la población, los mecanismos que desencadenan y mantienen la FA son inciertos. Aunque existen diversos tratamientos quirúrgicos y farmacológicos, el éxito de los tratamientos contra la FA es muy bajo. La causa de esta baja tasa de éxito de las diferentes terapias es que no existen criterios de selección de pacientes que permitan pronosticar qué terapia puede ser más efectiva para cada paciente. Una de las formas que se han propuesto para determinar el grado de gravedad de la arritmia en cada paciente y, por tanto, poder predecir qué tratamiento es el más apropiado es la medida de la organización auricular. Esta tesis doctoral se enmarca dentro de la determinación no invasiva del grado de organización espacial de la activación del miocardio auricular a partir del estudio de registros multiderivación del electrocardiograma de superficie (ECG). El ECG es una representación simplificada del campo eléctrico del corazón basada en las proyecciones de este campo eléctrico en 8 ejes. Esta simplificación es considerada como aceptable en el caso de ritmos no fibrilantes en los que la activación miocárdica puede ser modelada como un dipolo. Sin embargo, su validez no ha sido demostrada para el caso de ritmos fibrilantes en los cuales la asunción de un modelo dipolar es cuestionable. Uno de los objetivos de esta tesis ha sido la evaluación del electrocardiograma de superficie para la obtención de parámetros espaciales de las ondas de FA. Se compararon las representaciones tridimensionales de las ondas de FA registradas a partir de tres derivaciones ortogonales con las representaciones tridimensionales estimadas a partir del ECG, llegando a la conclusión de que estas representaciones estimadas no son fieles a las representaciones registradas. Los resultados de nuestro estudio ponen de manifiesto que la falta de d
Guillem Sanchez, MDLS. (2008). Activation patterns in atrial fibrillation: contributions of body surface potential mapping [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/3922
Palancia

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Nowadays the fibrillatory process is known to be provoked by the high-frequency reentrant activity of certain atrial regions that propagates the fibrillatory activity to the rest of the atrial tissue, and the electrical isolation of these key regions has demonstrated its effectiveness in terminating the fibrillatory process. The location of the dominant regions represents a major challenge in the diagnosis and treatment of this arrhythmia. With the aim to detect and locate the fibrillatory sources prior to surgical procedure, non-invasive methods have been developed such as body surface electrical mapping (BSPM) which allows to record with high spatial resolution the electrical activity on the torso surface or the electrocardiographic imaging (ECGI) which allows to non-invasively reconstruct the electrical activity in the atrial surface. Given the novelty of these systems, both technologies suffer from a lack of scientific knowledge about the physical and technical mechanisms that support their operation. Therefore, the aim of this thesis is to increase that knowledge, as well as studying the effectiveness of these technologies for the localization of dominant regions in patients with AF. First, it has been shown that BSPM systems are able to noninvasively identify atrial rotors by recognizing surface rotors after band-pass filtering. Furthermore, the position of such surface rotors is related to the atrial rotor location, allowing the distinction between left or right atrial rotors. Moreover, it has been found that the surface electrical maps in AF suffer a spatial smoothing effect by the torso conductor volume, so the surface electrical activity can be studied with a relatively small number of electrodes. Specifically, it has been seen that 12 uniformly distributed electrodes are sufficient for the correct identification of atrial dominant frequencies, while at least 32 leads are needed for non-invasive identification of atrial rotors. Secondly, the effect of narrowband filtering on the effectiveness of the location of reentrant patterns was studied. It has been found that this procedure allows isolating the reentrant electrical activity caused by the rotor, increasing the detection rate for both invasive and surface maps. However, the spatial smoothing caused by the regularization of the ECGI added to the temporal filtering causes a large increase in the spurious reentrant activity, making it difficult to detect real reentrant patterns. However, it has been found that maps provided by the ECGI without temporal filtering allow the correct detection of reentrant activity, so narrowband filtering should be applied for intracavitary or surface signal only. Finally, we studied the stability of the markers used to detect dominant regions in ECGI, such as frequency maps or the rotor presence. It has been found that in the presence of alterations in the conditions of the inverse problem, such as electrical or geometrical noise, these markers are significantly more stable than the ECGI signal morphology from which they are extracted. In addition, a new methodology for error reduction in the atrial spatial location based on the curvature of the curve L has been proposed. The results presented in this thesis showed that BSPM and ECGI systems allows to non-invasively locate the presence of high-frequency rotors, responsible for the maintenance of AF. This detection has been proven to be unambiguous and robust, and the physical and technical mechanisms that support this behavior have been studied. These results indicate that both non-invasive systems provide information of great clinical value in the treatment of AF, so their use can be helpful for selecting and planning atrial ablation procedures.
La fibrilación auricular (FA) es una de las arritmias cardiacas más frecuentes. Hoy en día se sabe que el proceso fibrilatorio está provocado por la actividad reentrante a alta frecuencia de ciertas regiones auriculares que propagan la actividad fibrilatoria en el resto del tejido auricular, y se ha demostrado que el aislamiento eléctrico de estas regiones dominantes permite detener el proceso fibrilatorio. La localización de las regiones dominantes supone un gran reto en el diagnóstico y tratamiento de la FA. Con el objetivo de poder localizar las fuentes fibrilatorias con anterioridad al procedimiento quirúrgico, se han desarrollado métodos no invasivos como la cartografía eléctrica de superficie (CES) que registra con gran resolución espacial la actividad eléctrica en la superficie del torso o la electrocardiografía por imagen (ECGI) que permite reconstruir la actividad eléctrica en la superficie auricular. Dada la novedad de estos sistemas, existe una falta de conocimiento científico sobre los mecanismos físicos y técnicos que sustentan su funcionamiento. Por lo tanto, el objetivo de esta tesis es aumentar dicho conocimiento, así como estudiar la eficacia de ambas tecnologías para la localización de regiones dominantes en pacientes con FA. En primer lugar, ha visto que los sistemas CES permiten identificar rotores auriculares mediante el reconocimiento de rotores superficiales tras el filtrado en banda estrecha. Además, la posición de los rotores superficiales está relacionada con la localización de dichos rotores, permitiendo la distinción entre rotores de aurícula derecha o izquierda. Por otra parte, se ha visto que los mapas eléctricos superficiales durante FA sufren una gran suavizado espacial por el efecto del volumen conductor del torso, lo que permite que la actividad eléctrica superficial pueda ser estudiada con un número relativamente reducido de electrodos. Concretamente, se ha visto que 12 electrodos uniformemente distribuidos son suficientes para una correcta identificación de frecuencias dominantes, mientras que son necesarios al menos 32 para una correcta identificación de rotores auriculares. Por otra parte, también se ha estudiado el efecto del filtrado en banda estrecha sobre la eficacia de la localización de patrones reentrantes. Así, se ha visto que este procedimiento permite aislar la actividad eléctrica reentrante provocada por el rotor, aumentando la tasa de detección tanto para señal obtenida de manera invasiva como para los mapas superficiales. No obstante, este filtrado temporal sobre la señal de ECGI provoca un gran aumento de la actividad reentrante espúrea que dificulta la detección de patrones reentrantes reales. Sin embargo, los mapas ECGI sin filtrado temporal permiten la detección correcta de la actividad reentrante, por lo el filtrado debería ser aplicado únicamente para señal intracavitaria o superficial. Por último, se ha estudiado la estabilidad de los marcadores utilizados en ECGI para detectar regiones dominantes, como son los mapas de frecuencia o la presencia de rotores. Se ha visto que en presencia de alteraciones en las condiciones del problema inverso, como ruido eléctrico o geométrico, estos marcadores son significativamente más estables que la morfología de la propia señal ECGI. Además, se ha propuesto una nueva metodología para la reducción del error en la localización espacial de la aurícula basado en la curvatura de la curva L. Los resultados presentados en esta tesis revelan que los sistemas de CES y ECGI permiten localizar de manera no invasiva la presencia de rotores de alta frecuencia. Esta detección es univoca y robusta, y se han estudiado los mecanismos físicos y técnicos que sustentan dicho comportamiento. Estos resultados indican que ambos sistemas no invasivos proporcionan información de gran valor clínico en el tratamiento de la FA, por lo que su uso puede ser de gran ayuda para la selección y planificaci
La fibril·lació auricular (FA) és una de les arítmies cardíaques més freqüents. Hui en dia es sabut que el procés fibrilatori està provocat per l'activitat reentrant de certes regions auriculars que propaguen l'activitat fibril·latoria a la resta del teixit auricular, i s'ha demostrat que l'aïllament elèctric d'aquestes regions dominants permet aturar el procés fibrilatori. La localització de les regions dominants suposa un gran repte en el diagnòstic i tractament d'aquesta arítmia. Amb l'objectiu de poder localitzar fonts fibril·latories amb anterioritat al procediment quirúrgic s'han desenvolupat mètodes no invasius com la cartografia elèctrica de superfície (CES) que registra amb gran resolució espacial l'activitat elèctrica en la superfície del tors o l'electrocardiografia per imatge (ECGI) que permet obtenir de manera no invasiva l'activitat elèctrica en la superfície auricular. Donada la relativa novetat d'aquests sistemes, existeix una manca de coneixement científic sobre els mecanismes físics i tècnics que sustenten el seu funcionament. Per tant, l'objectiu d'aquesta tesi és augmentar aquest coneixement, així com estudiar l'eficàcia d'aquestes tecnologies per a la localització de regions dominants en pacients amb FA. En primer lloc, s'ha vist que els sistemes CES permeten identificar rotors auriculars mitjançant el reconeixement de rotors superficials després del filtrat en banda estreta. A més, la posició dels rotors superficials està relacionada amb la localització d'aquests rotors, permetent la distinció entre rotors de aurícula dreta o esquerra. També s'ha vist que els mapes elèctrics superficials durant FA pateixen un gran suavitzat espacial per l'efecte del volum conductor del tors, el que permet que l'activitat elèctrica superficial pugui ser estudiada amb un nombre relativament reduït d'elèctrodes. Concretament, s'ha vist que 12 elèctrodes uniformement distribuïts són suficients per a una correcta identificació de freqüències dominants auriculars, mentre que són necessaris almenys 32 per a una correcta identificació de rotors auriculars. D'altra banda, també s'ha estudiat l'efecte del filtrat en banda estreta sobre l'eficàcia de la localització de patrons reentrants. Així, s'ha vist que aquest procediment permet aïllar l'activitat elèctrica reentrant provocada pel rotor, augmentant la taxa de detecció tant pel senyal obtingut de manera invasiva com per als mapes superficials. No obstant això, aquest filtrat temporal sobre el senyal de ECGI provoca un gran augment de l'activitat reentrant espúria que dificulta la detecció de patrons reentrants reals. A més, els mapes proporcionats per la ECGI sense filtrat temporal permeten la detecció correcta de l'activitat reentrant, per la qual cosa el filtrat hauria de ser aplicat únicament per a senyal intracavitària o superficial. Per últim, s'ha estudiat l'estabilitat dels marcadors utilitzats en ECGI per a detectar regions auriculars dominants, com són els mapes de freqüència o la presència de rotors. S'ha vist que en presència d'alteracions en les condicions del problema invers, com soroll elèctric o geomètric, aquests marcadors són significativament més estables que la morfologia del mateix senyal ECGI. A més, s'ha proposat una nova metodologia per a la reducció de l'error en la localització espacial de l'aurícula basat en la curvatura de la corba L. Els resultats presentats en aquesta tesi revelen que els sistemes de CES i ECGI permeten localitzar de manera no invasiva la presència de rotors d'alta freqüència. Aquesta detecció és unívoca i robusta, i s'han estudiat els mecanismes físics i tècnics que sustenten aquest comportament. Aquests resultats indiquen que els dos sistemes no invasius proporcionen informació de gran valor clínic en el tractament de la FA, pel que el seu ús pot ser de gran ajuda per a la selecció i planificació de procediments d'ablació auricular.
Rodrigo Bort, M. (2016). Non-invasive identification of atrial fibrillation drivers [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/75346
TESIS
Premiado

Responsable d’un quart des accidents vasculaires cérébraux, la fibrillation auriculaire (FA) est l’arythmie cardiaque la plus répandue. La thérapie d’ablation par cathéter (CA) est de plus en plus utilisée pour traiter la FA, mais ses effets sur le substrat cardiaque ne sont pas suffisamment compris, d’où un taux de réussite très variable. L’électrocardiogramme (ECG) à 12 voies représente un outil non invasif peu coûteux pour caractériser la FA à partir de l’activité électrique du cœur. Cependant, les prédicteurs classiques de l’issue de la CA présentent plusieurs inconvénients, notamment leur calcul manuel sur une seule voie de l’ECG. Cette thèse exploite explicitement le caractère multi-capteur de l’ECG au moyen de techniques de décomposition multivariées, démontrant qu’elles peuvent améliorer la puissance prédictive de certaines propriétés de l’ECG dans le cadre de la CA. L’amplitude des ondes fibrillatoires est corrélée avec le résultat de la CA, et traitée par une méthode multi-capteur basée sur l’analyse en composantes principales (PCA). Des variantes comme la PCA pondérée (WPCA) et la factorisation en matrices non négatives (NMF) peuvent aussi quantifier la variabilité spatio-temporelle de la FA sur l’ECG. La théorie de l’information permet également d’estimer le niveau de corrélation entre les voies de l’ECG, mis en relation avec le résultat de la CA grâce à des approches multi-capteurs. Enfin, une dernière ligne de recherche concerne la réponse ventriculaire manifestée sur la variabilité cardiaque. L’approche paramétrique de processus ponctuel est capable de souligner certaines propriétés de cette variabilité, améliorant ainsi la caractérisation de la FA
Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, and one of the main causes of stroke. Yet its thorough characterization and treatment remain an open issue. Despite the increasing popularity of the radiofrequency catheter ablation (CA) therapy, very little is known about its impact on heart substrate, leading to rather uncertain success rates. This calls for advanced signal processing tools for quantitatively assessing CA outcome. The surface 12-lead electrocardiogram (ECG), a noninvasive and cost-effective cardiac activity recording modality, provides valuable information about AF. However, some issues affect most of the standard CA outcome predictors, e.g., manual computation and limited single-lead perspective. This thesis aims at explicitly exploiting the ECG’s multilead character through multivariate decomposition tools, so as to enhance the role of some ECG features as CA outcome predictors. Fibrillatory wave amplitude is correlated with CA success in a multilead framework through principal component analysis (PCA). Multivariate approaches also enhance AF spatiotemporal variability measured on the ECG (e.g., weighted PCA, nonnegative matrix factorization), evidencing that the less repetitive the AF pattern, the less likely CA success. Information theory also quantifies interlead similarity between AF patterns, and is linked with CA outcome in a multilead framework. Another perspective focuses on the ventricular response as reflected on heart rate variability (HRV). Point process modeling can highlight certain HRV properties typical of AF in a parametric probabilistic context, helping AF pattern recognition

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is distinguished by fibrillating or trembling of the atrial muscle instead of normal contraction. Patients in AF have a much higher risk of stroke. AF is often driven by the left atrium (LA) and the diagnosis of AF is normally made from lead V1 in a 12-lead electrocardiogram (ECG). However, lead V1 is dominated by right atrial activity due to its proximal location to the right atrium (RA). Consequently it is not well understood how electrical activity from the LA contributes to the ECG. Studies of the AF mechanisms from the LA are typically based on invasive recording techniques. From a clinical point of view it is highly desirable to have an alternative, non-invasive characterisation of AF. The aim of this study was to investigate how the LA electrical activity was expressed on the body surface, and if it could be observed preferentially in different sites on the body surface. For this purpose, electrical activity of the heart from 20 patients in AF were recorded simultaneously using 64-lead body surface potential mapping (BSPM) and bipolar 10-electrode catheters located in the LA and coronary sinus (CS). Established AF characteristics such as amplitude, dominant frequency (DF) and spectral concentration (SC) were estimated and analysed. Furthermore, two novel AF characteristics (intracardiac DF power distribution, and body surface spectral peak type) were proposed to investigate the relationship between the BSPM and electrogram (EGM) recordings. The results showed that although in individual patients there were body surface sites that preferentially represented the AF characteristics estimated from the LA, those sites were not consistent across all patients. It was found that the left atrial activity could be detected in all body surface sites such that all sites had a dominant or non-dominant spectral peak corresponding to EGM DF. However, overall the results suggested that body surface site 22 (close to lead V1) was more closely representative of the CS activity, and site 49 (close to the posterior lower central right) was more closely representative of the left atrial activity. There was evidence of more accurate estimation of AF characteristics using additional electrodes to lead V1.

Accumulation or aggregation of amyloidogenic proteins in the brain plays a central role in neurodegenerative diseases. The most common and highly growing form of dementia in the elderly population is Alzheimer's disease (AD) followed by Parkinson's disease (PD). The major proteins associated are amyloid beta (Abeta) and alpha-synuclein (alpha-syn) in AD and PD, respectively. These proteins are released or found near the neuronal membranes in the brain. Consequently to understand the behavior of the proteins using a model membrane system becomes an important facet of understanding these diseases. Langmuir monolayer approach was used to study the surface chemistry and spectroscopy of Abeta (1-40), Abeta(1-42) and alpha-synuclein. Moreover, surface chemistry of a model protein namely, lysozyme was investigated. In recent times, quantum dots (QDs) are considered as potential probes for bio-imaging. These particles can be beneficial when it comes to the investigation of neurodegenerative diseases. The effect of nanoparticles, i.e., CdSe/ZnS QDs on Abeta (1-42) morphology was investigated. Nevertheless, it was observed that the capping ligand plays a significant role in the surface chemistry of QDs when mixed with or conjugated to Abeta (1-42). Surface pressure- and surface potential-area isotherms were used to characterize the lysozyme Langmuir monolayer. The compression-decompression cycles and stability measurements showed a homogeneous and stable monolayer at the air-water interface. Salt concentration in the subphase and pH of the subphase were parameters controlling homogeneity and stability of the Langmuir monolayer. In situ UV-vis and fluorescence spectroscopies were used to verify the homogeneity of the lysozyme monolayer, and to identify the chromophore residues in the lysozyme. Optimal experimental conditions were determined to prepare a homogeneous and stable lysozyme Langmuir monolayer. The surface chemistry and spectroscopy of the reduced lysozyme Langmuir monolayer were investigated at different pH values and were compared to a native lysozyme. It was established that the limiting molecular area of the reduced lysozyme was not subphase pH dependent as was found for the native one. To explain this result in terms of the conformation and orientation of the lysozyme Langmuir monolayer at various subphase pH values, we have used Infrared Reflection Absorption Spectroscopy (IRRAS). The interpretation of the results suggests a change in the conformation and orientation of the native lysozyme Langmuir monolayer with the subphase pH 3, 6 and 11. The surface chemistry of Abeta (1-40) and its interaction with the lipid raft Langmuir monolayer were examined where the stability of the lipid raft Langmuir monolayer came out as an essential parameter. Lipid raft Langmuir monolayer in the presence or absence of ganglioside GM1 having POPC as one of the phospholipids was found to be very unstable and collapsed within 26 min. Whereas, the phospholipid DPPG improved the stability of the monolayer significantly when cholesterol was used in excess. We have examined the surface and spectroscopic properties of Abeta (1-42) mixed with or conjugated to dihydrolipoic acid (DHLA)- and polyethylene glycol (PEG)- capped CdSe/ZnS QDs. Surface pressure-area isotherms, in situ UV-vis absorption, and fluorescence spectroscopy were used to characterize the Abeta (1-42) mixed with or conjugated to QDs at the air-water interface. The capping of QDs played a role in surface chemistry as was determined by surface pressure-area isotherms and spectroscopic properties of the Langmuir monolayer. Furthermore Abeta(1-42) was bioconjugated to DHLA-capped CdSe/ZnS QDs. Upon conjugation of Abeta (1-42) to DHLA-capped QDs, the sample was incubated at 37oC, the process of fibrillation was inhibited as compared with a sample where Abeta (1-42) was simply mixed with the QDs. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were employed for the analysis of the samples. The morphology of fibrils and reduction in number of fibrils was substantial in the case of Abeta(1-42) conjugated to QDs. Reduction in fibrillation was also confirmed using a Thioflavin T assay. Moreover, quenching of tyrosine signal was observed in presence of the QDs, which indicates an interaction of QDs to the tyrosine residue in Abeta (1-42). The Surface chemistry and spectroscopy of alpha-syn, which is a natively unstructured protein important in the neuropathology of PD was investigated. IRRAS was utilized to investigate its conformation, alpha-syn was found to form a Langmuir monolayer in alpha-helical conformation with its helical axis parallel to the air-water interface.

[EN] Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia, characterized by an uncoordinated atrial electrical activation, thus causing the atria to be unable to pump blood effectively. The prevalence of AF is expected to increase significantly in the next decades as the population ages. However, both the knowledge and the treatment of this arrhythmia still have to experiment a significant progress. Previous studies have reported that AF organization, which can be defined as the repetitiveness degree of the atrial activity pattern, correlates with the arrhythmia status as well as with the therapy outcome. Thus, estimating AF organization from surface electrocardiographic (ECG) recordings constitutes a very interesting approach because ECG recordings are easy and cheap to obtain. The objective of this doctoral thesis is to assess the use of a variety of nonlinear indices in the estimation of AF organization from single-lead noninvasive ECG recordings. Apart from the most common noninvasive AF organization estimators, such as Sample Entropy (SampEn) and the dominant atrial frequency (DAF), the following nonlinear indices have been studied: Fuzzy Entropy, Spectral Entropy, Lempel-Ziv Complexity and Hurst Exponents. Moreover, since the presence of noise and ventricular residuals affects the performance of nonlinear methods, the application of a strategy aimed at reducing these nuisances has been evaluated. Therefore, the application of these metrics over the atrial activity fundamental waveform, named the main atrial wave (MAW), has been proposed. In this doctoral thesis, the following scenarios involving AF organization have been considered: the prediction of paroxysmal AF spontaneous termination, the study of the earlier signs anticipating AF termination and the classification between paroxysmal and persistent AF from short ECG recordings. Firstly, the performance of the studied metrics discriminating events related to AF organization was tested making use of a reference database aimed at predicting AF spontaneous termination. In this study, most of the proposed indices provided higher accuracy than traditional AF organization estimators. Accuracy values higher than 90% were obtained with several indices. In particular, the generalized Hurst exponents of order 1 and 2, H(1) and H(2), achieved outstanding results, thus being selected for later studies in this thesis. Furthermore, the computation of H(2) depends on two critical parameters, namely, the analyzed interval length (L) and the maximum search window for self-similarities (tau). Hence, a study with 660 combinations on these two parameters was performed, together with the sampling frequency (fs) of the recording, in order to obtain their optimal combination in computing AF organization. On the other hand, previous works analyzing the spontaneous termination of AF have been only focused on the last 2 minutes preceding the termination. In contrast, a different scenario considering longer recordings to detect the earlier signs anticipating paroxysmal AF termination has been analyzed for the first time in this thesis. H(2) was selected for the study because of its highest accuracy in AF termination prediction. Additionally, the DAF and SampEn were also computed as references. Through this study it has been corroborated that AF organization only varies significantly within the last 3 minutes before spontaneous termination. As a consequence, the early prediction of paroxysmal AF spontaneous termination does not seem feasible through the current signal analysis tools. Finally, H(2) was applied in the classification between paroxysmal and persistent AF from short ECG recordings, achieving a higher diagnostic accuracy than DAF and SampEn. This result suggests that the analysis of ambulatory ECG recordings through H(2) could be a future alternative to the use of Holter ECG recordings in the classification between paroxysmal and persistent AF.
[ES] La fibrilación auricular (FA) es la arritmia más frecuente y se caracteriza por una actividad auricular descoordinada, que impide que las aurículas bombeen sangre de manera eficaz. Se espera que la prevalencia de la FA aumente significativamente en las próximas décadas debido al envejecimiento de la población. Sin embargo, tanto el conocimiento relativo a esta arritmia como su tratamiento son todavía mejorables. Estudios previos han relacionado la organización de la FA, que se puede definir como el grado de repetitividad de la actividad auricular, con el estado de la arritmia o su respuesta al tratamiento. Además, la estimación de la organización de la FA a partir de registros electrocardiográficos (ECG) de superficie resulta especialmente interesante porque su obtención es sencilla y barata. El objetivo de esta tesis doctoral es evaluar el uso de distintos índices no lineales para estimar la organización de la FA a partir del ECG. Además de los estimadores no invasivos de organización más comunes, como la entropía muestral (SampEn) y la frecuencia auricular dominante (DAF), se han estudiado los siguientes métodos no lineales: la entropía borrosa, la entropía espectral, la complejidad Lempel-Ziv y los exponentes de Hurst. Además, se ha estudiado el uso de una estrategia destinada a la reducción del ruido y los residuos de actividad ventricular para mejorar el desempeño de métodos no lineales. Así, los índices estudiados también se han aplicado sobre la forma de onda fundamental de la actividad auricular, conocida como la onda auricular principal (MAW). Se han considerado los siguientes escenarios relacionados con la organización de la FA: la predicción de la terminación espontánea de la FA paroxística, el estudio de los primeros indicios de terminación espontánea de la FA y la clasificación entre FA paroxística y FA persistente a partir de registros ECG de corta duración. Primero, se estudió la capacidad de los índices estudiados para distinguir eventos relacionados con la organización de la FA mediante el análisis de una base de datos de referencia para la predicción de su terminación espontánea. La mayoría de los índices propuestos consiguieron una mayor precisión que los estimadores tradicionales de organización. Así, varios de los índices obtuvieron una precisión superior al 90% en la predicción de la terminación espontánea de la FA. En particular, los exponentes de Hurst generalizados de orden 1 y 2, H(1) y H(2), lograron los mejores resultados de clasificación. Puesto que el cálculo de H(2) depende de dos parámetros críticos, la longitud del intervalo analizado (L) y el tamaño máximo de la ventana donde buscar similitudes (tau), se llevó a cabo un estudio con 660 combinaciones de esos dos parámetros junto con la frecuencia de muestreo (fs) del registro para determinar el uso óptimo de este índice. Por otra parte, los trabajos previos que han estudiado la terminación espontánea de la FA se han centrado en los últimos 2 minutos antes de la terminación. Por contra, en esta tesis doctoral se han estudiado por primera vez registros de mayor duración para detectar los primeros indicios de la terminación de la FA. Para ello, se eligió el uso de H(2) por su alta precisión en la predicción de la terminación de la FA. Además, la DAF y SampEn se calcularon como referencias. En este estudio se ha comprobado que la organización de la FA solamente presenta variaciones significativas en los últimos 3 minutos antes de su terminación espontánea. Por ello, la predicción temprana de la terminación no parece posible con los medios actuales de análisis de la señal. Por último, se aplicó H(2) para clasificar entre FA paroxística y FA persistente a partir de ECGs de corta duración, obteniendo una mayor precisión diagnóstica que la DAF y SampEn. Este resultado sugiere que el análisis de ECGs ambulatorios por medio de H(2) puede ser en el futuro una alte
[CAT] La fibril·lació auricular (FA) és l'arítmia més freqüent i es caracteritza per una activitat auricular descoordinada, que impedix que les aurícules bomben sang de manera eficaç. S'espera que la prevalença de la FA augmente significativament en les pròximes dècades a causa de l'envelliment de la població. No obstant això, tant el coneixement relatiu a esta arítmia com el seu tractament són encara millorables. Estudis previs han relacionat l'organització de la FA, que es pot definir com el grau de repetitivitat de l'activitat auricular, amb l'estat de l'arítmia o la seua resposta al tractament. A més, l'estimació de l'organització de la FA a partir de registres electrocardiogràfics (ECG) de superfície resulta especialment interessant perquè la seua obtenció és senzilla i barata. L'objectiu d'esta tesi doctoral és avaluar l'ús de distints índexs no lineals en l'estimació de l'organització de la FA a partir de l'ECG de superfície. A més dels estimadors no invasius d'organització més comuns, com l'entropia mostral (SampEn) i la freqüència auricular dominant (DAF), s'han estudiat els següents mètodes no lineals: l'entropia borrosa, l'entropia espectral, la complexitat Lempel-Ziv i els exponents de Hurst. A més, s'ha estudiat l'ús d'una estratègia destinada a la reducció del soroll i els residus d'activitat ventricular per a millorar la seua capacitat d'estimar l'organització. Així, doncs, els índexs estudiats també s'han aplicat sobre la forma d'onda fonamental de l'activitat auricular, coneguda com l'onda auricular principal (MAW). S'han considerat els següents escenaris relacionats amb l'organització de la FA: la predicció de la terminació espontània de la FA paroxística, l'estudi dels primers indicis de terminació espontània de la FA i la classificació entre FA paroxística i FA persistent a partir de registres ECG de curta duració. Primer, es va estudiar la capacitat dels índexs estudiats per a distingir esdeveniments relacionats amb l'organització de la FA per mitjà de l'anàlisi d'una base de dades de referència per a la predicció de la seua terminació espontània. La majoria dels índexs proposats van aconseguir una major precisió que els estimadors tradicionals d'organització de la FA. Així, alguns dels índexs van obtindre una precisió superior al 90% en la predicció de la terminació espontània de la FA. En particular, els exponents de Hurst generalitzats d'orde 1 i 2, H(1) i H(2), van aconseguir els millors resultats de classificació. Com el càlcul de H(2) depén de dos paràmetres crítics, la longitud de l'interval analitzat (L) i la grandària màxima de la finestra on buscar similituds (tau), es va dur a terme un estudi amb 660 combinacions d'eixos dos paràmetres junt amb la freqüència de mostratge (fs) del registre per a determinar la combinació òptima de valors per a estimar l'organització de la FA. D'altra banda, els treballs previs que han estudiat la terminació espontània de la FA s'han centrat en els últims 2 minuts abans de la terminació. Per contra, en esta tesi doctoral s'han estudiat per primera vegada registres de major duració amb l'objectiu de detectar els primers indicis de la terminació de la FA. Es va triar l'ús de H(2) per a este estudi per la seua alta precisió en la predicció de la terminació de la FA. A més, la DAF i SampEn es van calcular com a referències. En este estudi s'ha comprovat que l'organització de la FA només presenta variacions significatives en els últims 3 minuts abans de la seua terminació espontània. Per això, la predicció primerenca de la terminació no pareix possible amb els mitjans actuals d'anàlisi del senyal. Finalment, es va aplicar H(2) per a classificar entre FA paroxística i FA persistent a partir d'ECGs de curta duració, obtenint una millor precisió diagnòstica que amb la DAF i SampEn. Este resultat suggerix que l'anàlisi d'ECGs ambulatoris per mitjà de H(2) pot ser en e
Julián Seguí, M. (2015). Study on the non-linear metrics contribution to estimate atrial fibrillation organization from the surface electrocardiogram [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/56150
TESIS

Responsable d'un quart des accidents vasculaires cérébraux, la fibrillation auriculaire (FA) est l'arythmie cardiaque la plus répandue. La thérapie d'ablation par cathéter (CA) est de plus en plus utilisée pour traiter la FA, mais ses effets sur le substrat cardiaque ne sont pas suffisamment compris, d'où un taux de réussite très variable. L'électrocardiogramme (ECG) à 12 voies représente un outil non invasif peu coûteux pour caractériser la FA à partir de l'activité électrique du cœur. Cependant, les prédicteurs classiques de l'issue de la CA présentent plusieurs inconvénients, notamment leur calcul manuel sur une seule voie de l'ECG. Cette thèse exploite explicitement le caractère multi-capteur de l'ECG au moyen de techniques de décomposition multivariées, démontrant qu'elles peuvent améliorer la puissance prédictive de certaines propriétés de l'ECG dans le cadre de la CA. L'amplitude des ondes fibrillatoires est corrélée avec le résultat de la CA, et traitée par une méthode multi-capteur basée sur l'analyse en composantes principales (PCA). Des variantes comme la PCA pondérée (WPCA) et la factorisation en matrices non négatives (NMF) peuvent aussi quantifier la variabilité spatio-temporelle de la FA sur l'ECG. La théorie de l'information permet également d'estimer le niveau de corrélation entre les voies de l'ECG, mis en relation avec le résultat de la CA grâce à des approches multi-capteurs. Enfin, une dernière ligne de recherche concerne la réponse ventriculaire manifestée sur la variabilité cardiaque. L'approche paramétrique de processus ponctuel est capable de souligner certaines propriétés de cette variabilité, améliorant ainsi la caractérisation de la FA.

Atrial arrhythmias are the most prevalent sustained cardiac arrhythmias. Rates of hospitalisation and costs incurred to healthcare organisations are increasing in epidemic proportions. Despite this, the mechanisms of the transition from sinus rhythm to arrhythmic states are not well understood. The high level of regional electrical heterogeneity observed in the atria is thought to contribute towards the high prevalence of atrial arrhythmias. However, current computer models of the intact human atria only account for a small degree of this regional electrical heterogeneity, and do not include descriptions of the pacemaker regions of the sinoatrial node and the atrioventricular node. In this project, a new computational model of the intact 3D human atria is developed. First, a new single cell model to simulate the electrical action potential of the human atrial myocyte is developed. This model more accurately simulated the experimentally observed properties of human atrial action potentials than previous models. A family of electrically heterogeneous models describing the major regions within the atria is then developed, including those of the sinoatrial- and atrioventricular- nodes. This set of regional cell models represents the most expansive and complete set currently available. It is demonstrated that the large range of different electrical properties results in a large range of action potential morphology and duration within the atria. Models of the effect of sympathetic and parasympathetic regulation on the electrical AP of the models of the atrial working myocardium and the pacemaker regions were also incorporated. This demonstrated that sympathetic regulation can increase the pacing rate of the sinoatrial node and the atrio-ventricular node, and has a complex dose dependent effect on the atrial working myocardium. Four distinct models of the effects of atrial fibrillation induced remodelling on the atrial working myocardium are developed. These characterised the effect of remodelling of IKur on the overall changes in action potential morphology and duration observed. It is shown that the presence or absence of remodelling of this channel accounts for two distinct observed morphologies. A previous 3D anatomical model of the human atria is improved. First, detailed anatomical models for the sinoatrial node and the atrioventricular node are incorporated into the model. Second, it is further segmented to include regions for the pulmonary veins, atrio-ventricular ring, atrial septum and sinoatrial node block zone. This model is used to investigate the effects of sympathetic and parasympathetic regulation in the 3D atria. Finally, a detailed investigation of the underlying mechanisms of atrial fibrillation in the 3D atria, and the effect of electrical remodelling on the behaviour of atrial fibrillation, is performed using the detailed 3D model. This work represents a significant advance in 3D human atrial modelling. The anatomical model incorporates a greater level of complexity than previous models, and for the first time allowed investigation of the pacemaking mechanisms in the 3D intact human atria. The atrial fibrillation protocols are more physiologically relevant than previous models and have elucidated the roles that electrophysiological remodelling, electrical heterogeneity and structural anisotropy play in the development and maintenance of atrial fibrillation.

Osteoarthritis (OA) is the commonest condition to affect synovial joints, but although any synovial joint can be affected, most studies of pathology relate to large joints (knees and hips). OA involves the whole joint and pathological alterations typically occur in all joint tissues. Established OA is characterized by a mixture of tissue loss and new tissue production resulting in focal loss of articular hyaline cartilage together with bone remodelling and osteophyte formation. Articular cartilage may show increased thickness in the earliest stages of OA with increased numbers of hypertrophic chondrocytes, followed by progressive decline in matrix components, thickness, and chondrocyte number. Surface fibrillation and vertical clefts become evident in mid- to end-stage OA and eventual complete loss of cartilage can occur, predominantly in maximum load-bearing regions, with subsequent eburnation and furrowing of bone. Bone remodelling may lead to alteration of bone shape and variable trabecular thickness in subchondral bone, whilst subchondral microfractures may result in localized osteonecrosis, fibrosis, and ‘cysts’. Endochondral ossification of new fibrocartilage produced predominantly at the joint margin produces characteristic bony osteophytes. The synovium shows areas of hyperplasia with varying amounts of lymphocyte aggregates and inclusion of osteochondral ‘loose’ bodies, and the outer fibrous capsule thickens to help stabilize the compromised joint. Synovial fluid increases in volume but decreases in viscosity. Periarticular changes include type II muscle atrophy and enthesophytes.

Islet amyloid polypeptide (IAPP) fibrillation has been commonly associated with the exacerbation of type 2 diabetes prognosis. Consequently, inhibition of IAPP fibrillation to minimize β-cell cytotoxicity is an important approach towards β-cell preservation and type 2 diabetes management. In this study, three tetrapeptides, TNGQ, MANT, and YMSV, were identified as potential IAPP fibrillation inhibitors. The potential anti-fibrillation mechanisms of these tetrapeptides were monitored using thioflavin T (ThT) fluorescence assay, circular dichroism (CD) spectroscopy, dynamic light scattering (DLS) and molecular docking. ThT fluorescence kinetics and microscopy, as well as transmission electron microscopy, showed that TNGQ was the most effective inhibitor based on the absence of normal IAPP fibrillar morphology and alluded to its IAPP fibrillar disaggregatory potential. CD spectroscopy showed that TNGQ maintained the α-helical conformation of monomeric IAPP, while DLS confirmed the presence of varying fibrillation species. Molecular docking showed that interactions between TNGQ and MANT and monomeric IAPP favoured hydrogen bonding and electrostatic interactions. Furthermore, TNGQ bound at the IAPP surface, unlike YMSV, which had the highest docking score but interact mainly through hydrophobic interactions in the IAPP core. These findings indicate the potential of TNGQ in the development of peptide-based anti-fibrillation and antidiabetic nutraceuticals.