12,153 research outputs found
Endogenous measures for contextualising large-scale social phenomena: a corpus-based method for mediated public discourse
This work presents an interdisciplinary methodology for developing endogenous measures of group membership through analysis of pervasive linguistic patterns in public discourse. Focusing on political discourse, this work critiques the conventional approach to the study of political participation, which is premised on decontextualised, exogenous measures to characterise groups. Considering the theoretical and empirical weaknesses of decontextualised approaches to large-scale social phenomena, this work suggests that contextualisation using endogenous measures might provide a complementary perspective to mitigate such weaknesses.
This work develops a sociomaterial perspective on political participation in mediated discourse as affiliatory action performed through language. While the affiliatory function of language is often performed consciously (such as statements of identity), this work is concerned with unconscious features (such as patterns in lexis and grammar). This work argues that pervasive patterns in such features that emerge through socialisation are resistant to change and manipulation, and thus might serve as endogenous measures of sociopolitical contexts, and thus of groups.
In terms of method, the work takes a corpus-based approach to the analysis of data from the Twitter messaging service whereby patterns in users’ speech are examined statistically in order to trace potential community membership. The method is applied in the US state of Michigan during the second half of 2018—6 November having been the date of midterm (i.e. non-Presidential) elections in the United States. The corpus is assembled from the original posts of 5,889 users, who are nominally geolocalised to 417 municipalities. These users are clustered according to pervasive language features. Comparing the linguistic clusters according to the municipalities they represent finds that there are regular sociodemographic differentials across clusters. This is understood as an indication of social structure, suggesting that endogenous measures derived from pervasive patterns in language may indeed offer a complementary, contextualised perspective on large-scale social phenomena
High-throughput Tools and Techniques to Investigate Environmental Effects on Aging Behaviors in Caenorhabditis elegans
Aging is modulated by genetic and environmental cues; however, it is difficult to study how these perturbations modulate the aging process in a robust, high-throughput manner. Methods to gather large-scale behavioral data for aging studies are labor-intensive, lack individual-level resolution, or lack precise spatiotemporal environmental control. In addition, tools to analyze large-scale behavioral data sets are difficult to scale, unable to be broadly applied across complex environments, or fail to detect subtle behavioral changes.
In this thesis I develop tools to enable robust, microfluidic culture and behavioral analysis of C. elegans to examine how environmental cues, such as dietary restriction, influence longevity and behavior with age. In Aim 1, I engineer a robust pipeline for the long-term longitudinal culture and behavioral monitoring of C. elegans in aging studies with precise spatiotemporal environmental control. In Aim 2, I develop a flexible deep learning based pipeline for detecting and extracting postural information from large-scale behavioral datasets across heterogeneous environments. In Aim 3, I characterize how the full behavioral repertoire of individuals change with age, along with examining how these age-related behavioral changes are modulated by different dietary restriction regimes. The completion of this thesis provides 1) a new toolset to robustly explore how genetic or environmental effects influence longevity and healthspan, 2) a flexible pipeline for analyzing large-scale behavioral data in C. elegans, and 3) insight into how environmental perturbations influence health through age-related changes in behavior.Ph.D
Changes in soil fertility and microbial communities following cultivation of native grassland in Horqin Sandy Land, China: a 60-year chronosequence
Background: Grassland conversion to cropland is a prevailing change of land use in traditionally nomadic areas, especially in the Mongolian Plateau. We investigated the effects of grassland conversion followed by continuous cultivation on soil properties and microbial community characteristics in Horqin Sandy Land, a typical agro-pastoral transition zone of Northern China. Soil samples were collected from the topsoil (upper 20 cm) across a 60-year cultivation chronosequence (5, 15, 25, 35 and 60 years) and unconverted native grassland. Soil physico-chemical properties were determined and high-throughput sequencing was used to assess microbial community diversity and composition. Results: Grassland cultivation resulted in changes to soil properties in both the short and longer term. Initially, it significantly increased soil bulk density (BD), electrical conductivity (EC), soil total nitrogen (TN), available phosphorus (AP) and available potassium (AK) concentrations, while reducing soil water content (SWC) and soil organic carbon content (SOC). Over the next 35–55 years of continuous cultivation, the trend for most of these characteristics was of reversion towards values nearer to those of native grassland, except for SOC which remained highly depleted. Cultivation of grassland substantially altered soil microbial communities at phylum level but there was no significant difference in microbial α-diversity between native grassland and any cropland. However, soil bacterial and fungal community structures at phylum level in the croplands of all cultivation years were different from those in the native grasslands. Heatmaps further revealed that bacterial and fungal structures in cropland tended to become more similar to native grassland after 15 and 25 years of cultivation, respectively. Redundancy analysis indicated that SOC, EC and BD were primary determinants of microbial community composition and diversity. Conclusions: These findings suggest that agricultural cultivation of grassland has considerable effects on soil fertility and microbial characteristics of Horqin Sandy Land. Intensive high-yield forage grass production is proposed as an alternative to avoid further native grassland reclamation, while meeting the grazing development needs in the ethnic minority settlements of eco-fragile regions
Countermeasures for the majority attack in blockchain distributed systems
La tecnología Blockchain es considerada como uno de los paradigmas informáticos más importantes posterior al Internet; en función a sus características únicas que la hacen ideal para registrar, verificar y administrar información de diferentes transacciones. A pesar de esto, Blockchain se enfrenta a diferentes problemas de seguridad, siendo el ataque del 51% o ataque mayoritario uno de los más importantes. Este consiste en que uno o más mineros tomen el control de al menos el 51% del Hash extraído o del cómputo en una red; de modo que un minero puede manipular y modificar arbitrariamente la información registrada en esta tecnología. Este trabajo se enfocó en diseñar e implementar estrategias de detección y mitigación de ataques mayoritarios (51% de ataque) en un sistema distribuido Blockchain, a partir de la caracterización del comportamiento de los mineros. Para lograr esto, se analizó y evaluó el Hash Rate / Share de los mineros de Bitcoin y Crypto Ethereum, seguido del diseño e implementación de un protocolo de consenso para controlar el poder de cómputo de los mineros. Posteriormente, se realizó la exploración y evaluación de modelos de Machine Learning para detectar software malicioso de tipo Cryptojacking.DoctoradoDoctor en Ingeniería de Sistemas y Computació
A Finite Element-Inspired Hypergraph Neural Network: Application to Fluid Dynamics Simulations
An emerging trend in deep learning research focuses on the applications of
graph neural networks (GNNs) for mesh-based continuum mechanics simulations.
Most of these learning frameworks operate on graphs wherein each edge connects
two nodes. Inspired by the data connectivity in the finite element method, we
present a method to construct a hypergraph by connecting the nodes by elements
rather than edges. A hypergraph message-passing network is defined on such a
node-element hypergraph that mimics the calculation process of local stiffness
matrices. We term this method a finite element-inspired hypergraph neural
network, in short FEIH()-GNN. We further equip the proposed network with
rotation equivariance, and explore its capability for modeling unsteady fluid
flow systems. The effectiveness of the network is demonstrated on two common
benchmark problems, namely the fluid flow around a circular cylinder and
airfoil configurations. Stabilized and accurate temporal roll-out predictions
can be obtained using the -GNN framework within the interpolation
Reynolds number range. The network is also able to extrapolate moderately
towards higher Reynolds number domain out of the training range
Decoding spatial location of attended audio-visual stimulus with EEG and fNIRS
When analyzing complex scenes, humans often focus their attention on an object at a particular spatial location in the presence of background noises and irrelevant visual objects. The ability to decode the attended spatial location would facilitate brain computer interfaces (BCI) for complex scene analysis. Here, we tested two different neuroimaging technologies and investigated their capability to decode audio-visual spatial attention in the presence of competing stimuli from multiple locations. For functional near-infrared spectroscopy (fNIRS), we targeted dorsal frontoparietal network including frontal eye field (FEF) and intra-parietal sulcus (IPS) as well as superior temporal gyrus/planum temporal (STG/PT). They all were shown in previous functional magnetic resonance imaging (fMRI) studies to be activated by auditory, visual, or audio-visual spatial tasks. We found that fNIRS provides robust decoding of attended spatial locations for most participants and correlates with behavioral performance. Moreover, we found that FEF makes a large contribution to decoding performance. Surprisingly, the performance was significantly above chance level 1s after cue onset, which is well before the peak of the fNIRS response.
For electroencephalography (EEG), while there are several successful EEG-based algorithms, to date, all of them focused exclusively on auditory modality where eye-related artifacts are minimized or controlled. Successful integration into a more ecological typical usage requires careful consideration for eye-related artifacts which are inevitable. We showed that fast and reliable decoding can be done with or without ocular-removal algorithm. Our results show that EEG and fNIRS are promising platforms for compact, wearable technologies that could be applied to decode attended spatial location and reveal contributions of specific brain regions during complex scene analysis
Learning disentangled speech representations
A variety of informational factors are contained within the speech signal and a single short recording of speech reveals much more than the spoken words. The best method to extract and represent informational factors from the speech signal ultimately depends on which informational factors are desired and how they will be used. In addition, sometimes methods will capture more than one informational factor at the same time such as speaker identity, spoken content, and speaker prosody.
The goal of this dissertation is to explore different ways to deconstruct the speech signal into abstract representations that can be learned and later reused in various speech technology tasks. This task of deconstructing, also known as disentanglement, is a form of distributed representation learning. As a general approach to disentanglement, there are some guiding principles that elaborate what a learned representation should contain as well as how it should function. In particular, learned representations should contain all of the requisite information in a more compact manner, be interpretable, remove nuisance factors of irrelevant information, be useful in downstream tasks, and independent of the task at hand. The learned representations should also be able to answer counter-factual questions.
In some cases, learned speech representations can be re-assembled in different ways according to the requirements of downstream applications. For example, in a voice conversion task, the speech content is retained while the speaker identity is changed. And in a content-privacy task, some targeted content may be concealed without affecting how surrounding words sound. While there is no single-best method to disentangle all types of factors, some end-to-end approaches demonstrate a promising degree of generalization to diverse speech tasks.
This thesis explores a variety of use-cases for disentangled representations including phone recognition, speaker diarization, linguistic code-switching, voice conversion, and content-based privacy masking. Speech representations can also be utilised for automatically assessing the quality and authenticity of speech, such as automatic MOS ratings or detecting deep fakes. The meaning of the term "disentanglement" is not well defined in previous work, and it has acquired several meanings depending on the domain (e.g. image vs. speech). Sometimes the term "disentanglement" is used interchangeably with the term "factorization". This thesis proposes that disentanglement of speech is distinct, and offers a viewpoint of disentanglement that can be considered both theoretically and practically
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
New functions of platelet C3G: Involvement in TPO-regulation, ischemia-induced angiogenesis and tumor metastasis
[ES] Las GTPasas son proteínas que regulan una gran variedad de procesos celulares,
entre los que cabe destacar la proliferación, la diferenciación celular y la apoptosis.
Estas proteínas alternan entre dos confirmaciones: una activa o unida a GTP y una
inactiva o unida a GDP. El intercambio de GDP por GTP esta catalizado por un grupo
de proteínas denominadas GEF (factores intercambiadores de nucleótidos de guanina),
mientras que las proteínas GAP (proteínas activadoras de la actividad GTPasa) inhiben
a la GTPasa. C3G es un GEF para varias GTPasas de la familia de Ras, principalmente
de Rap1, R-Ras y TC21, y para una GTPasa de la familia de Rho, TC10. Mediante el
uso de modelos animales que expresan de manera específica en plaquetas y
megacariocitos o bien C3G (tgC3G), o bien una forma mutante de C3G (caracterizada
por la pérdida del dominio catalítico, tgC3GCat), nuestro grupo ha demostrado la
participación de C3G en la diferenciación megacariocítica, así como en la regulación de
la función hemostática de las plaquetas. En concreto, las plaquetas tgC3G presentan
una mayor activación y agregación plaquetaria, que se correlaciona con tiempos de
sangrado significativamente inferiores en los ratones tgC3G, además de un incremento
en la formación de trombos en modelos in vivo. La sobreexpresión de C3G plaquetario,
también genera una alteración en la secreción de los gránulos-α, caracterizada por la
retención del factor de crecimiento del endotelio vascular (VEGF) y de trombospondina-
1 (TSP-1) en el citoplasma de las plaquetas, dando lugar a un secretoma netamente
proangiogénico. Como resultado de la mayor capacidad proangiogénica de las
plaquetas que sobreexpresan C3G, los ratones tgC3G mostraron un crecimiento tumoral
más rápido en dos modelos heterotópicos de implantación tumoral. Además, la proteína
C3G plaquetaria promueve la metástasis pulmonar de células de melanoma (B16-F10).
Sin embargo, la expresión transgénica de C3G no altera los recuentos plaquetarios en
sangre periférica.
En esta Tesis, hemos profundizado en el papel de C3G en la megacariopoyesis,
en la angiogénesis inducida por isquemia y en la metástasis tumoral. Para ello, hemos
desarrollado un modelo animal adicional (C3G-KO), en el cual C3G se encuentra
específicamente delecionado en megacariocitos (Mk). Al igual que lo observado en
ratones tgC3G, los animales C3G-KO tampoco mostraron diferencias ni en el número
de Mk en médula ósea, ni en los recuentos plaquetarios en sangre periférica. Sin
embargo, la deleción de C3G resultó en una mayor maduración megacariocítica in vitro
cuando las médulas óseas fueron cultivas en medio enriquecido con trombopoyetina (TPO) junto con un cocktail de citocinas, sugiriendo un posible papel de C3G en una
megacariopoyesis patológica.
En base a esto, hemos analizamos el papel de C3G en dos modelos in vivo de
megacariopoyesis patológica: la inyección de TPO y la mielosupresión inducida por 5-
Fluoruracilo (5-FU). La inyección intravenosa de TPO estimula la megacariopoyesis,
incrementando los niveles plaquetarios; mientras que el 5-FU induce la depleción de la
médula ósea alrededor del séptimo día tas la inyección, lo que va seguido de un
profundo incremento en el recuento plaquetario, proceso conocido como rebote
plaquetario (platelet rebound) tras 10-15 días de tratamiento
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