17,920 research outputs found
Optimizations of Autoencoders for Analysis and Classification of Microscopic In Situ Hybridization Images
Currently, analysis of microscopic In Situ Hybridization images is done
manually by experts. Precise evaluation and classification of such microscopic
images can ease experts' work and reveal further insights about the data. In
this work, we propose a deep-learning framework to detect and classify areas of
microscopic images with similar levels of gene expression. The data we analyze
requires an unsupervised learning model for which we employ a type of
Artificial Neural Network - Deep Learning Autoencoders. The model's performance
is optimized by balancing the latent layers' length and complexity and
fine-tuning hyperparameters. The results are validated by adapting the
mean-squared error (MSE) metric, and comparison to expert's evaluation.Comment: 9 pages; 9 figure
Pollution-induced community tolerance in freshwater biofilms – from molecular mechanisms to loss of community functions
Exposure to herbicides poses a threat to aquatic biofilms by affecting their community structure, physiology and function. These changes render biofilms to become more tolerant, but on the downside community tolerance has ecologic costs. A concept that addresses induced community tolerance to a pollutant (PICT) was introduced by Blanck and Wängberg (1988). The basic principle of the concept is that microbial communities undergo pollution-induced succession when exposed to a pollutant over a long period of time, which changes communities structurally and functionally and enhancing tolerance to the pollutant exposure. However, the mechanisms of tolerance and the ecologic consequences were hardly studied up to date. This thesis addresses the structural and functional changes in biofilm communities and applies modern molecular methods to unravel molecular tolerance mechanisms.
Two different freshwater biofilm communities were cultivated for a period of five weeks, with one of the communities being contaminated with 4 μg L-1 diuron. Subsequently, the communities were characterized for structural and functional differences, especially focusing on their crucial role of photosynthesis. The community structure of the autotrophs was assessed using HPLC-based pigment analysis and their functional alterations were investigated using Imaging-PAM fluorometry to study photosynthesis and community oxygen profiling to determine net primary production. Then, the molecular fingerprints of the communities were measured with meta-transcriptomics (RNA-Seq) and GC-based community metabolomics approaches and analyzed with respect to changes in their molecular functions. The communities were acute exposed to diuron for one hour in a dose-response design, to reveal a potential PICT and uncover related adaptation to diuron exposure. The combination of apical and molecular methods in a dose-response design enabled the linkage of functional effects of diuron exposure and underlying molecular mechanisms based on a sensitivity analysis.
Chronic exposure to diuron impaired freshwater biofilms in their biomass accrual. The contaminated communities particularly lost autotrophic biomass, reflected by the decrease in specific chlorophyll a content. This loss was associated with a change in the molecular fingerprint of the communities, which substantiates structural and physiological changes. The decline in autotrophic biomass could be due to a primary loss of sensitive autotrophic organisms caused by the selection of better adapted species in the course of chronic exposure. Related to this hypothesis, an increase in diuron tolerance has been detected in the contaminated communities and molecular mechanisms facilitating tolerance have been found. It was shown that genes of the photosystem, reductive-pentose phosphate cycle and arginine metabolism were differentially expressed among the communities and that an increased amount of potential antioxidant degradation products was found in the contaminated communities. This led to the hypothesis that contaminated communities may have adapted to oxidative stress, making them less sensitive to diuron exposure. Moreover, the photosynthetic light harvesting complex was altered and the photoprotective xanthophyll cycle was increased in the contaminated communities. Despite these adaptation strategies, the loss of autotrophic biomass has been shown to impair primary production. This impairment persisted even under repeated short-term exposure, so that the tolerance mechanisms cannot safeguard primary production as a key function in aquatic systems.:1. The effect of chemicals on organisms and their functions .............................. 1
1.1 Welcome to the anthropocene .......................................................................... 1
1.2 From cellular stress responses to ecosystem resilience ................................... 3
1.2.1 The individual pursuit for homeostasis ....................................................... 3
1.2.2 Stability from diversity ................................................................................. 5
1.3 Community ecotoxicology - a step forward in monitoring the effects of chemical
pollution? ................................................................................................................. 6
1.4 Functional ecotoxicological assessment of microbial communities ................... 9
1.5 Molecular tools – the key to a mechanistic understanding of stressor effects
from a functional perspective in microbial communities? ...................................... 12
2. Aims and Hypothesis ......................................................................................... 14
2.1 Research question .......................................................................................... 14
2.2 Hypothesis and outline .................................................................................... 15
2.3 Experimental approach & concept .................................................................. 16
2.3.1 Aquatic freshwater biofilms as model community ..................................... 16
2.3.2 Diuron as model herbicide ........................................................................ 17
2.3.3 Experimental design ................................................................................. 18
3. Structural and physiological changes in microbial communities after chronic
exposure - PICT and altered functional capacity ................................................. 21
3.1 Introduction ..................................................................................................... 21
3.2 Methods .......................................................................................................... 23
3.2.1 Biofilm cultivation ...................................................................................... 23
3.2.2 Dry weight and autotrophic index ............................................................. 23
3.2.4 Pigment analysis of periphyton ................................................................. 23
3.2.4.1 In-vivo pigment analysis for community characterization ....................... 24
3.2.4.2 In-vivo pigment analysis based on Imaging-PAM fluorometry ............... 24
3.2.4.3 In-vivo pigment fluorescence for tolerance detection ............................. 26
3.2.4.4 Ex-vivo pigment analysis by high-pressure liquid-chromatography ....... 27
3.2.5 Community oxygen metabolism measurements ....................................... 28
3.3 Results and discussion ................................................................................... 29
3.3.1 Comparison of the structural community parameters ............................... 29
3.3.2 Photosynthetic activity and primary production of the communities after
selection phase ................................................................................................. 33
3.3.3 Acquisition of photosynthetic tolerance .................................................... 34
3.3.4 Primary production at exposure conditions ............................................... 36
3.3.5 Tolerance detection in primary production ................................................ 37
3.4 Summary and Conclusion ........................................................................... 40
4. Community gene expression analysis by meta-transcriptomics ................... 41
4.1 Introduction to meta-transcriptomics ............................................................... 41
4.2. Methods ......................................................................................................... 43
4.2.1 Sampling and RNA extraction................................................................... 43
4.2.2 RNA sequencing analysis ......................................................................... 44
4.2.3 Data assembly and processing................................................................. 45
4.2.4 Prioritization of contigs and annotation ..................................................... 47
4.2.5 Sensitivity analysis of biological processes .............................................. 48
4.3 Results and discussion ................................................................................... 48
4.3.1 Characterization of the meta-transcriptomic fingerprints .......................... 49
4.3.2 Insights into community stress response mechanisms using trend analysis
(DRomic’s) ......................................................................................................... 51
4.3.3 Response pattern in the isoform PS genes .............................................. 63
4.5 Summary and conclusion ................................................................................ 65
5. Community metabolome analysis ..................................................................... 66
5.1 Introduction to community metabolomics ........................................................ 66
5.2 Methods .......................................................................................................... 68
5.2.1 Sampling, metabolite extraction and derivatisation................................... 68
5.2.2 GC-TOF-MS analysis ............................................................................... 69
5.2.3 Data processing and statistical analysis ................................................... 69
5.3 Results and discussion ................................................................................... 70
5.3.1 Characterization of the metabolic fingerprints .......................................... 70
5.3.2 Difference in the metabolic fingerprints .................................................... 71
5.3.3 Differential metabolic responses of the communities to short-term exposure
of diuron ............................................................................................................ 73
5.4 Summary and conclusion ................................................................................ 78
6. Synthesis ............................................................................................................. 79
6.1 Approaches and challenges for linking molecular data to functional
measurements ...................................................................................................... 79
6.2 Methods .......................................................................................................... 83
6.2.1 Summary on the data ............................................................................... 83
6.2.2 Aggregation of molecular data to index values (TELI and MELI) .............. 83
6.2.3 Functional annotation of contigs and metabolites using KEGG ................ 83
6.3 Results and discussion ................................................................................... 85
6.3.1 Results of aggregation techniques ........................................................... 85
6.3.2 Sensitivity analysis of the different molecular approaches and endpoints 86
6.3.3 Mechanistic view of the molecular stress responses based on KEGG
functions ............................................................................................................ 89
6.4 Consolidation of the results – holistic interpretation and discussion ............... 93
6.4.1 Adaptation to chronic diuron exposure - from molecular changes to
community effects.............................................................................................. 93
6.4.2 Assessment of the ecological costs of Pollution-induced community
tolerance based on primary production ............................................................. 94
6.5 Outlook ............................................................................................................ 9
Electrically-evoked responses for retinal prostheses are differentially altered depending on ganglion cell types in outer retinal neurodegeneration caused by Crb1 gene mutation
BackgroundMicroelectronic prostheses for artificial vision stimulate neurons surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the quality of prosthetic vision substantially varies across subjects, maybe due to different levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes are remarkably diverse, prosthetic studies have primarily used retinal degeneration (rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model which has Crb1 mutation.MethodsWe first investigated age-dependent histological changes of wild-type (wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch clamping to record spiking responses of ON, OFF and direction selective (DS) types of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were analyzed in comparison with those of wt RGCs in terms of individual RGC spiking patterns, populational characteristics, and spiking consistency across trials.ResultsIn the histological examination, the rd8 mice showed partial retinal foldings, but the outer nuclear layer thicknesses remained comparable to those of the wt mice, indicating the early-stage of RP. Although spiking patterns of each RGC type seemed similar to those of the wt retinas, correlation levels between electric vs. light response features were different across the two mouse models. For example, in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of the rd8 mice showed the same/opposite correlation polarity with those of wt mice, respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas showed a positive correlation with their direction selectivity indices (r = 0.40), while those of the wt retinas were negatively correlated (r = −0.90). Lastly, the spiking timing consistencies of late responses were largely decreased in both ON and OFF RGCs in the rd8 than the wt retinas, whereas no significant difference was found across DS RGCs of the two models.ConclusionOur results indicate the electric response features are altered depending on RGC types even from the early-stage RP caused by Crb1 mutation. Given the various degeneration patterns depending on mutation genes, our study suggests the importance of both genotype- and RGC type-dependent analyses for retinal prosthetic research
Chiral active fluids: Odd viscosity, active turbulence, and directed flows of hydrodynamic microrotors
While the number of publications on rotating active matter has rapidly increased in recent years, studies on purely hydrodynamically interacting rotors on the microscale are still rare, especially from the perspective of particle based hydrodynamic simulations. The work presented here targets to fill this gap. By means of high-performance computer simulations, performed in a highly parallelised fashion on graphics processing units, the dynamics of ensembles of up to 70,000 rotating colloids immersed in an explicit mesoscopic solvent consisting out of up to 30 million fluid particles, are investigated. Some of the results presented in this thesis have been worked out in collaboration with experimentalists, such that the theoretical considerations developed in this thesis are supported by experiments, and vice versa. The studied system, modelled in order to resemble the essential physics of the experimentally realisable system, consists out of rotating magnetic colloidal particles, i.e., (micro-)rotors, rotating in sync to an externally applied magnetic field, where the rotors solely interact via hydrodynamic and steric interactions. Overall, the agreement between simulations and experiments is very good, proving that hydrodynamic interactions play a key role in this and related systems.
While already an isolated rotating colloid is driven out of equilibrium, only collections of two or more rotors have experimentally shown to be able to convert the rotational energy input into translational dynamics in an orbital rotating fashion. The rotating colloids inject circular flows into the fluid, such that detailed balance is broken, and it is not a priori known whether equilibrium properties of colloids can be extended to isolated rotating colloids. A joint theoretical and experimental analysis of isolated, pairs, and small groups of hydrodynamically interacting rotors is given in chapter 2. While the translational dynamics of isolated rotors effectively resemble the dynamics of non-rotating colloids, the orbital rotation of pairs of rotors can be described with leading order hydrodynamics and a two-dimensional analogy of Faxén’s law is derived.
In chapter 3, a homogeneously distributed ensemble of rotors (bulk) as a realisation of a chiral active fluid is studied and it is explicitly shown computationally and experimentally that it carries odd viscosity. The mutual orbital translation of rotors and an increase of the effective solvent viscosity with rotor density lead to a non-monotonous behaviour of the average translational velocity. Meanwhile, the rotor suspension bears a finite osmotic compressibility resulting from the long-ranged nature of hydrody- namic interactions such that rotational and odd stresses are transmitted through the solvent also at small and intermediate rotor densities. Consequently, density inhomogeneities predicted for chiral active fluids with odd viscosity can be found and allow for an explicit measurement of odd viscosity in simulations and experiments. At intermediate densities, the collective dynamics shows the emergence of multi-scale vortices and chaotic motion which is identified as active turbulence with a self-similar power-law decay in the energy spectrum, showing that the injected energy on the rotor scale is transported to larger scales, similar to the inverse energy cascade of clas- sical two-dimensional turbulence. While either odd viscosity or active turbulence have been reported in chiral active matter previously, the system studied here shows that the emergence of both simultaneously is possible resulting from the osmotic compressibility and hydrodynamic mediation of odd and active stresses. The collective dynamics of colloids rotating out of phase, i.e., where a constant torque instead of a constant angular velocity is applied, is shown to be qualitatively very similar. However, at smaller densities, local density inhomogeneities imply position dependent angular velocities of the rotors resulting from inter-rotor friction.
While the friction of a quasi-2D layer of active colloids with the substrate is often not easily modifiable in experiments, the incorporation of substrate friction into the simulation models typically implies a considerable increase in computational effort. In chapter 4, a very efficient way of incorporating the friction with a substrate into a two-dimensional multiparticle collision dynamics solvent is introduced, allowing for an explicit investigation of the influences of substrate on active dynamics. For the rotor fluid, it is explicitly shown that the influence of the substrate friction results in a cutoff of the hydrodynamic interaction length, such that the maximum size of the formed vortices is controlled by the substrate friction, also resulting in a cutoff in the energy spectrum, because energy is taken out of the system at the respective length. These findings are in agreement with the experiments.
Since active particles in confinement are known to organise in states of collective dynamics, ensembles of rotationally actuated colloids are studied in circular confinement and in the presence of periodic obstacle lattices in chapters 5 and 6, respectively. The results show that the chaotic active turbulent transport of rotors in suspension can be enhanced and guided resulting from edge flows generated at the boundaries, as has recently been reported for a related chiral active system. The consequent collective rotor dynamics can be regarded as a superposition of active turbulent and imposed flows, leading to on average stationary flows. In contrast to the bulk dynamics, the imposed flows inject additional energy into the system on the long length scales, and the same scaling behaviour of the energy spectrum as in bulk is only obtained if the energy injection scales, due to the mutual generation of rotor translational dynamics throughout the system and the edge flows, are well separated. The combination of edge flow and entropic layering at the boundaries leads to oscillating hydrodynamic stresses and consequently to an oscillating vorticity profile. In the presence of odd viscosity, this consequently leads to non-trivial steady-state density modulations at the boundary, resulting from a balance of osmotic pressure and odd stresses.
Relevant for the efficient dispersion and mixing of inert particles on the mesoscale by means of active turbulent mixing powered by rotors, a study of the dynamics of a binary mixture consisting out of rotors and passive particles is presented in chapter 7. Because the rotors are not self-propelled, but the translational dynamics is induced by the surrounding rotors, the passive particles, which do not inject further energy into the system, are transported according to the same mechanism as the rotors. The collective dynamics thus resembles the pure rotor bulk dynamics at the respective density of only rotors. However, since no odd stresses act between the passive particles, only mutual rotor interactions lead to odd stresses leading to the accumulation of rotors in the regions of positive vorticity. This density increase is associated with a pressure increase, which balances the odd stresses acting on the rotors. However, the passive particles are only subject to the accumulation induced pressure increase such that these particles are transported into the areas of low rotor concentration, i.e., the regions of negative vorticity. Under conditions of sustained vortex flow, this results in segregation of both particle types.
Since local symmetry breaking can convert injected rotational into translational energy, microswimmers can be constructed out of rotor materials when a suitable breaking of symmetry is kept in the vicinity of a rotor. One hypothetical realisation, i.e., a coupled rotor pair consisting out of two rotors of opposite angular velocity and of fixed distance, termed a birotor, are studied in chapter 8. The birotor pumps the fluid into one direction and consequently translates into the opposite direction, and creates a flow field reminiscent of a source doublet, or sliplet flow field. Fixed in space the birotor might be an interesting realisation of a microfluidic pump. The trans- lational dynamics of a birotor can be mapped onto the active Brownian particle model for single swimmers. However, due to the hydrodynamic interactions among the rotors, the birotor ensemble dynamics do not show the emergence of stable motility induced clustering. The reason for this is the flow created by birotor in small aggregates which effectively pushes further arriving birotors away from small aggregates, which eventually are all dispersed by thermal fluctuations
Modelling uncertainties for measurements of the H → γγ Channel with the ATLAS Detector at the LHC
The Higgs boson to diphoton (H → γγ) branching ratio is only 0.227 %, but this
final state has yielded some of the most precise measurements of the particle. As
measurements of the Higgs boson become increasingly precise, greater import is
placed on the factors that constitute the uncertainty. Reducing the effects of these
uncertainties requires an understanding of their causes. The research presented
in this thesis aims to illuminate how uncertainties on simulation modelling are
determined and proffers novel techniques in deriving them.
The upgrade of the FastCaloSim tool is described, used for simulating events in
the ATLAS calorimeter at a rate far exceeding the nominal detector simulation,
Geant4. The integration of a method that allows the toolbox to emulate the
accordion geometry of the liquid argon calorimeters is detailed. This tool allows
for the production of larger samples while using significantly fewer computing
resources.
A measurement of the total Higgs boson production cross-section multiplied
by the diphoton branching ratio (σ × Bγγ) is presented, where this value was
determined to be (σ × Bγγ)obs = 127 ± 7 (stat.) ± 7 (syst.) fb, within agreement
with the Standard Model prediction. The signal and background shape modelling
is described, and the contribution of the background modelling uncertainty to the
total uncertainty ranges from 18–2.4 %, depending on the Higgs boson production
mechanism.
A method for estimating the number of events in a Monte Carlo background
sample required to model the shape is detailed. It was found that the size of
the nominal γγ background events sample required a multiplicative increase by
a factor of 3.60 to adequately model the background with a confidence level of
68 %, or a factor of 7.20 for a confidence level of 95 %. Based on this estimate,
0.5 billion additional simulated events were produced, substantially reducing the
background modelling uncertainty.
A technique is detailed for emulating the effects of Monte Carlo event generator
differences using multivariate reweighting. The technique is used to estimate the
event generator uncertainty on the signal modelling of tHqb events, improving the
reliability of estimating the tHqb production cross-section. Then this multivariate
reweighting technique is used to estimate the generator modelling uncertainties
on background V γγ samples for the first time. The estimated uncertainties were
found to be covered by the currently assumed background modelling uncertainty
Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico
Valve replacement remains as the standard therapeutic option for aortic
stenosis patients, aiming at abolishing pressure overload and triggering
myocardial reverse remodeling. However, despite the instant hemodynamic
benefit, not all patients show complete regression of myocardial hypertrophy,
being at higher risk for adverse outcomes, such as heart failure. The current
comprehension of the biological mechanisms underlying an incomplete reverse
remodeling is far from complete. Furthermore, definitive prognostic tools and
ancillary therapies to improve the outcome of the patients undergoing valve
replacement are missing. To help abridge these gaps, a combined myocardial
(phospho)proteomics and pericardial fluid proteomics approach was followed,
taking advantage of human biopsies and pericardial fluid collected during
surgery and whose origin anticipated a wealth of molecular information
contained therein.
From over 1800 and 750 proteins identified, respectively, in the myocardium
and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated
proteins were detected. Gene annotation and pathway enrichment analyses,
together with discriminant analysis, are compatible with a scenario of increased
pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by
complement activity and other extrinsic factors, such as death receptor
activators), acute-phase response, immune system activation and fibrosis.
Specific validation of some targets through immunoblot techniques and
correlation with clinical data pointed to complement C3 β chain, Muscle Ring
Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation
regulated kinase 1A (DYRK1A) as potential markers of an incomplete
response. In addition, kinase prediction from phosphoproteome data suggests
that the modulation of casein kinase 2, the family of IκB kinases, glycogen
synthase kinase 3 and DYRK1A may help improve the outcome of patients
undergoing valve replacement. Particularly, functional studies with DYRK1A+/-
cardiomyocytes show that this kinase may be an important target to treat
cardiac dysfunction, provided that mutant cells presented a different response
to stretch and reduced ability to develop force (active tension).
This study opens many avenues in post-aortic valve replacement reverse
remodeling research. In the future, gain-of-function and/or loss-of-function
studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic
targets. Besides, clinical studies in larger cohorts will bring definitive proof of
complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de
referência para doentes com estenose aórtica e visa a eliminação da
sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica.
Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes
apresentam regressão completa da hipertrofia do miocárdio, ficando com maior
risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os
mecanismos biológicos subjacentes a uma remodelagem reversa incompleta
ainda não são claros. Além disso, não dispomos de ferramentas de
prognóstico definitivos nem de terapias auxiliares para melhorar a condição
dos pacientes indicados para substituição da válvula. Para ajudar a resolver
estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica
para a caracterização, respetivamente, do miocárdio e do líquido pericárdico
foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em
ambiente cirúrgico.
Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio
e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90
proteínas desreguladas foram detetadas. As análises de anotação de genes,
de enriquecimento de vias celulares e discriminativa corroboram um cenário de
aumento da expressão de genes pro-hipertróficos e de síntese proteica, um
sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular
(potencialmente acelerada pela atividade do complemento e por outros fatores
extrínsecos que ativam death receptors), com ativação da resposta de fase
aguda e do sistema imune, assim como da fibrose.
A validação de alguns alvos específicos através de immunoblot e correlação
com dados clínicos apontou para a cadeia β do complemento C3, a Muscle
Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation
regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta
incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma,
sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a
glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição
dos pacientes indicados para intervenção. Em particular, a avaliação funcional
de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo
importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes
responderam de forma diferente ao estiramento e mostraram uma menor
capacidade para desenvolver força (tensão ativa).
Este estudo levanta várias hipóteses na investigação da remodelagem reversa.
No futuro, estudos de ganho e/ou perda de função realizados em
cardiomiócitos isolados ou em modelos animais de banding-debanding da
aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos
encontrados. Além disso, estudos clínicos em coortes de maior dimensão
trarão conclusões definitivas quanto ao valor de prognóstico do complemento
C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
Diagnosis of Pneumonia Using Deep Learning
Artificial intelligence (AI) is an area of computer science that emphasizes the creation of intelligent machines or software that work and react like humans. Some of the activities computers with artificial intelligence are designed for include, Speech, recognition, Learning, Planning and Problem solving. Deep learning is a collection of algorithms used in machine learning, It is part of a broad family of methods used for machine learning that are based on learning representations of data. Deep learning is a technique used to produce Pneumonia detection and classification models using x-ray imaging for rapid and easy detection and identification of pneumonia. In this thesis, we review ways and mechanisms to use deep learning techniques to produce a model for Pneumonia detection. The goal is find a good and effective way to detect pneumonia based on X-rays to help the chest doctor in decision-making easily and accuracy and speed. The model will be designed and implemented, including both Dataset of image and Pneumonia detection through the use of Deep learning algorithms based on neural networks. The test and evaluation will be applied to a range of chest x-ray images and the results will be presented in detail and discussed. This thesis uses deep learning to detect pneumonia and its classification
Modeling Uncertainty for Reliable Probabilistic Modeling in Deep Learning and Beyond
[ES] Esta tesis se enmarca en la intersección entre las técnicas modernas de Machine Learning, como las Redes Neuronales Profundas, y el modelado probabilístico confiable. En muchas aplicaciones, no solo nos importa la predicción hecha por un modelo (por ejemplo esta imagen de pulmón presenta cáncer) sino también la confianza que tiene el modelo para hacer esta predicción (por ejemplo esta imagen de pulmón presenta cáncer con 67% probabilidad). En tales aplicaciones, el modelo ayuda al tomador de decisiones (en este caso un médico) a tomar la decisión final. Como consecuencia, es necesario que las probabilidades proporcionadas por un modelo reflejen las proporciones reales presentes en el conjunto al que se ha asignado dichas probabilidades; de lo contrario, el modelo es inútil en la práctica. Cuando esto sucede, decimos que un modelo está perfectamente calibrado.
En esta tesis se exploran tres vias para proveer modelos más calibrados. Primero se muestra como calibrar modelos de manera implicita, que son descalibrados por técnicas de aumentación de datos. Se introduce una función de coste que resuelve esta descalibración tomando como partida las ideas derivadas de la toma de decisiones con la regla de Bayes. Segundo, se muestra como calibrar modelos utilizando una etapa de post calibración implementada con una red neuronal Bayesiana. Finalmente, y en base a las limitaciones estudiadas en la red neuronal Bayesiana, que hipotetizamos que se basan en un prior mispecificado, se introduce un nuevo proceso estocástico que sirve como distribución a priori en un problema de inferencia Bayesiana.[CA] Aquesta tesi s'emmarca en la intersecció entre les tècniques modernes de Machine Learning, com ara les Xarxes Neuronals Profundes, i el modelatge probabilístic fiable. En moltes aplicacions, no només ens importa la predicció feta per un model (per ejemplem aquesta imatge de pulmó presenta càncer) sinó també la confiança que té el model per fer aquesta predicció (per exemple aquesta imatge de pulmó presenta càncer amb 67% probabilitat). En aquestes aplicacions, el model ajuda el prenedor de decisions (en aquest cas un metge) a prendre la decisió final. Com a conseqüència, cal que les probabilitats proporcionades per un model reflecteixin les proporcions reals presents en el conjunt a què s'han assignat aquestes probabilitats; altrament, el model és inútil a la pràctica. Quan això passa, diem que un model està perfectament calibrat.
En aquesta tesi s'exploren tres vies per proveir models més calibrats. Primer es mostra com calibrar models de manera implícita, que són descalibrats per tècniques d'augmentació de dades. S'introdueix una funció de cost que resol aquesta descalibració prenent com a partida les idees derivades de la presa de decisions amb la regla de Bayes. Segon, es mostra com calibrar models utilitzant una etapa de post calibratge implementada amb una xarxa neuronal Bayesiana. Finalment, i segons les limitacions estudiades a la xarxa neuronal Bayesiana, que es basen en un prior mispecificat, s'introdueix un nou procés estocàstic que serveix com a distribució a priori en un problema d'inferència Bayesiana.[EN] This thesis is framed at the intersection between modern Machine Learning techniques, such as Deep Neural Networks, and reliable probabilistic modeling. In many machine learning applications, we do not only care about the prediction made by a model (e.g. this lung image presents cancer) but also in how confident is the model in making this prediction (e.g. this lung image presents cancer with 67% probability). In such applications, the model assists the decision-maker (in this case a doctor) towards making the final decision. As a consequence, one needs that the probabilities provided by a model reflects the true underlying set of outcomes, otherwise the model is useless in practice. When this happens, we say that a model is perfectly calibrated.
In this thesis three ways are explored to provide more calibrated models. First, it is shown how to calibrate models implicitly, which are decalibrated by data augmentation techniques. A cost function is introduced that solves this decalibration taking as a starting point the ideas derived from decision making with Bayes' rule. Second, it shows how to calibrate models using a post-calibration stage implemented with a Bayesian neural network. Finally, and based on the limitations studied in the Bayesian neural network, which we hypothesize that came from a mispecified prior, a new stochastic process is introduced that serves as a priori distribution in a Bayesian inference problem.Maroñas Molano, J. (2022). Modeling Uncertainty for Reliable Probabilistic Modeling in Deep Learning and Beyond [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/181582TESI
Epilepsy Mortality: Leading Causes of Death, Co-morbidities, Cardiovascular Risk and Prevention
a reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected ... Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by ..
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