12,901 research outputs found
Norsk rå kumelk, en kilde til zoonotiske patogener?
The worldwide emerging trend of eating “natural” foods, that has not been
processed, also applies for beverages. According to Norwegian legislation, all
milk must be pasteurized before commercial sale but drinking milk that has
not been heat-treated, is gaining increasing popularity. Scientist are warning
against this trend and highlights the risk of contracting disease from milkborne
microorganisms. To examine potential risks associated with drinking
unpasteurized milk in Norway, milk- and environmental samples were
collected from dairy farms located in south-east of Norway. The samples
were analyzed for the presence of specific zoonotic pathogens; Listeria
monocytogenes, Campylobacter spp., and Shiga toxin-producing Escherichia
coli (STEC). Cattle are known to be healthy carriers of these pathogens, and
Campylobacter spp. and STEC have a low infectious dose, meaning that
infection can be established by ingesting a low number of bacterial cells. L.
monocytogenes causes one of the most severe foodborne zoonotic diseases,
listeriosis, that has a high fatality rate. All three pathogens have caused milk
borne disease outbreaks all over the world, also in Norway.
During this work, we observed that the prevalence of the three examined
bacteria were high in the environment at the examined farms. In addition, 7%
of the milk filters were contaminated by STEC, 13% by L. monocytogenes and
4% by Campylobacter spp. Four of the STEC isolates detected were eaepositive,
which is associated with the capability to cause severe human
disease. One of the eae-positive STEC isolates were collected from a milk
filter, which strongly indicate that Norwegian raw milk may contain potential
pathogenic STEC.
To further assess the possibilities of getting ill by STEC after consuming raw
milk, we examined the growth of the four eae-positive STEC isolates in raw milk at different temperatures. All four isolates seemed to have ability to multiply in raw milk at 8°C, and one isolate had significant growth after 72 hours. Incubation at 6°C seemed to reduce the number of bacteria during the
first 24 hours before cell death stopped. These findings highlight the
importance of stable refrigerator temperatures, preferable < 4°C, for storage
of raw milk.
The L. monocytogenes isolates collected during this study show genetic
similarities to isolates collected from urban and rural environmental
locations, but different clones were predominant in agricultural
environments compared to clinical and food environments. However, the
results indicate that the same clone can persist in a farm over time, and that
milk can be contaminated by L. monocytogenes clones present in farm
environment.
Despite testing small volumes (25 mL) of milk, we were able to isolate both
STEC and Campylobacter spp. directly from raw milk. A proportion of 3% of
the bulk tank milk and teat milk samples were contaminated by
Campylobacter spp. and one STEC was isolated from bulk tank milk. L
monocytogenes was not detected in bulk tank milk, nor in teat milk samples.
The agricultural evolvement during the past decades have led to larger
production units and new food safety challenges. Dairy cattle production in
Norway is in a current transition from tie-stall housing with conventional
pipeline milking systems, to modern loose housing systems with robotic
milking. The occurrence of the three pathogens in this project were higher in
samples collected from farms with loose housing compared to those with tiestall
housing.
Pasteurization of cow’s milk is a risk reducing procedure to protect
consumers from microbial pathogens and in most EU countries, commercial
distribution of unpasteurized milk is legally restricted. Together, the results
presented in this thesis show that the animal housing may influence the level
of pathogenic bacteria in the raw milk and that ingestion of Norwegian raw
cow’s milk may expose consumers to pathogenic bacteria which can cause
severe disease, especially in children, elderly and in persons with underlying
diseases. The results also highlight the importance of storing raw milk at low
temperatures between milking and consumption.Å spise mat som er mindre prosessert og mer «naturlig» er en pågående
trend i Norge og i andre deler av verden. Interessen for å drikke melk som
ikke er varmebehandlet, såkalt rå melk, er også økende. I Norge er det påbudt
å pasteurisere melk før kommersielt salg for å beskytte forbrukeren mot
sykdomsfremkallende mikroorganismer. Fagfolk advarer mot å drikke rå
melk, og påpeker risikoen for å bli syk av patogene bakterier som kan finnes i
melken.
I denne avhandlingen undersøker vi den potensielle risikoen det medfører å
drikke upasteurisert melk fra Norge. I tillegg til å samle inn tankmelk- og
speneprøver fra melkegårder i sørøst Norge, samlet vi også miljøprøver fra
de samme gårdene for å kartlegge forekomst og for å identifisere potensielle
mattrygghetsrisikoer i melkeproduksjonen. Alle prøvene ble analysert for de
zoonotiske sykdomsfremkallende bakteriene Listeria monocytogenes,
Campylobacter spp., og Shiga toksin-produserende Escherichia coli (STEC).
Kyr kan være friske smittebærere av disse bakteriene, som dermed kan
etablere et reservoar på gårdene. Bakteriene kan overføres fra gårdsmiljøet
til melkekjeden og dermed utfordre mattryggheten. Disse bakteriene har
forårsaket melkebårne sykdomsutbrudd over hele verden, også i Norge.
Campylobacter spp. og STEC har lav infeksiøs dose, som vil si at man kan bli
syk selv om man bare inntar et lavt antall bakterieceller. L. monocytogenes
kan gi sykdommen listeriose, en av de mest alvorlige matbårne zoonotiske
sykdommene vi har i den vestlige verden.
Resultater fra denne oppgaven viser en høy forekomst av de tre patogenene i
gårdsmiljøet. I tillegg var 7% av melkefiltrene vi testet positive for STEC, 13%
positive for L. monocytogenes og 4% positive for Campylobacter spp.. Fire av
STEC isolatene bar genet for Intimin, eae, som er ansett som en viktig
virulensfaktor som øker sjansen for alvorlig sykdom. Ett av de eae-positive
isolatene ble funnet i et melkefilter, noe som indikerer at norsk rå melk kan
inneholde patogene STEC. For å videre vurdere risikoen for å bli syk av STEC
fra rå melk undersøkte vi hvordan de fire eae-positive isolatene vokste i rå
melk lagret ved forskjellige temperaturer. For alle isolatene økte antall
bakterier etter lagring ved 8°C, og for et isolat var veksten signifikant. Etter
lagring ved 6°C ble antallet bakterier redusert de første 24 timene, deretter
stoppet reduksjonen i antall bakterier. Disse resultatene viser hvor viktig det
er å ha stabil lav lagringstemperatur for rå melk, helst < 4°C.
L. monocytogenes isolatene som ble samlet inn fra melkegårdene viste
genetiske likheter med isolater samlet inn fra urbane og rurale miljøer rundt
omkring i Norge. Derimot var kloner som dominerte i landbruksmiljøet
forskjellige fra kliniske isolater og isolater fra matproduksjonslokaler. Videre
så man at en klone kan persistere på en gård over tid og at melk kan
kontamineres av L. monocytogenes kloner som er til stede i gårdsmiljøet.
Til tross for små testvolum av tankmelken (25 mL) fant vi både STEC og
Campylobacter spp. i melkeprøvene. 3% av tankmelkprøvene og
speneprøvene var positive for Campylobacter spp. og ett STEC isolat ble
funnet i tankmelk. L. monocytogenes ble ikke funnet direkte i melkeprøvene.
Landbruket i Norge er i stadig utvikling der besetningene blir større, men
færre. Melkebesetningene er midt i en overgang der tradisjonell oppstalling
med melking på bås byttes ut med løsdriftssystemer og melkeroboter.
Forekomsten av de tre patogenene funnet i denne studien var høyere i
besetningene med løsdrift sammenliknet med besetningene som hadde
melkekyrne oppstallet på bås.
Pasteurisering er et viktig forebyggende tiltak for å beskytte konsumenter fra
mikrobielle patogener, og i de fleste EU-land er kommersielt salg av rå melk
juridisk begrenset. Denne studien viser at oppstallingstype kan påvirke
nivåene av patogene bakterier i gårdsmiljøet og i rå melk. Inntak av rå melk
kan eksponere forbruker for patogene bakterier som kan gi alvorlig sykdom,
spesielt hos barn, eldre og personer med underliggende sykdommer.
Resultatene underbygger viktigheten av å pasteurisere melk for å sikre
mattryggheten, og at det er avgjørende å lagre rå melk ved kontinuerlig lave
temperaturer for å forebygge vekst av zoonotiske patogener
Neuroanatomical and gene expression features of the rabbit accessory olfactory system. Implications of pheromone communication in reproductive behaviour and animal physiology
Mainly driven by the vomeronasal system (VNS), pheromone
communication is involved in many species-specific fundamental innate socio-sexual behaviors such as mating and
fighting, which are essential for animal reproduction and survival. Rabbits are a unique model for studying
chemocommunication due to the discovery of the rabbit mammary pheromone, but paradoxically there has been a
lack of knowledge regarding its VNS pathway. In this work, we aim at filling this gap by approaching the system
from an integrative point of view, providing extensive anatomical and genomic data of the rabbit VNS, as well as
pheromone-mediated reproductive and behavioural studies. Our results build strong foundation for further
translational studies which aim at implementing the use of pheromones to improve animal production and welfare
OLIG2 neural progenitor cell development and fate in Down syndrome
Down syndrome (DS) is caused by triplication of human chromosome 21 (HSA21) and is the most common genetic form of intellectual disability. It is unknown precisely how triplication of HSA21 results in the intellectual disability, but it is thought that the global transcriptional dysregulation caused by trisomy 21 perturbs multiple aspects of neurodevelopment that cumulatively contribute to its etiology. While the characteristics associated with DS can arise from any of the genes triplicated on HSA21, in this work we focus on oligodendrocyte transcription factor 2 (OLIG2). The progeny of neural progenitor cells (NPCs) expressing OLIG2 are likely to be involved in many of the cellular changes underlying the intellectual disability in DS. To explore the fate of OLIG2+ neural progenitors, we took advantage of two distinct models of DS, the Ts65Dn mouse model and induced pluripotent stem cells (iPSCs) derived from individuals with DS. Our results from these two systems identified multiple perturbations in development in the cellular progeny of OLIG2+ NPCs. In Ts65Dn, we identified alterations in neurons and glia derived from the OLIG2 expressing progenitor domain in the ventral spinal cord. There were significant differences in the number of motor neurons and interneurons present in the trisomic lumbar spinal cord depending on age of the animal pointing both to a neurodevelopment and a neurodegeneration phenotype in the Ts65Dn mice. Of particular note, we identified changes in oligodendrocyte (OL) maturation in the trisomic mice that are dependent on spatial location and developmental origin. In the dorsal corticospinal tract, there were significantly fewer mature OLs in the trisomic mice, and in the lateral funiculus we observed the opposite phenotype with more mature OLs being present in the trisomic animals. We then transitioned our studies into iPSCs where we were able to pattern OLIG2+ NPCs to either a spinal cord-like or a brain-like identity and study the OL lineage that differentiated from each progenitor pool. Similar to the region-specific dysregulation found in the Ts65Dn spinal cord, we identified perturbations in trisomic OLs that were dependent on whether the NPCs had been patterned to a brain-like or spinal cord-like fate. In the spinal cord-like NPCs, there was no difference in the proportion of cells expressing either OLIG2 or NKX2.2, the two transcription factors whose co-expression is essential for OL differentiation. Conversely, in the brain-like NPCs, there was a significant increase in OLIG2+ cells in the trisomic culture and a decrease in NKX2.2 mRNA expression. We identified a sonic hedgehog (SHH) signaling based mechanism underlying these changes in OLIG2 and NKX2.2 expression in the brain-like NPCs and normalized the proportion of trisomic cells expressing the transcription factors to euploid levels by modulating the activity of the SHH pathway. Finally, we continued the differentiation of the brain-like and spinal cord-like NPCs to committed OL precursor cells (OPCs) and allowed them to mature. We identified an increase in OPC production in the spinal cord-like trisomic culture which was not present in the brain-like OPCs. Conversely, we identified a maturation deficit in the brain-like trisomic OLs that was not present in the spinal cord-like OPCs. These results underscore the importance of regional patterning in characterizing changes in cell differentiation and fate in DS. Together, the findings presented in this work contribute to the understanding of the cellular and molecular etiology of the intellectual disability in DS and in particular the contribution of cells differentiated from OLIG2+ progenitors
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The Epidemiology and Genetic Architecture of Vitamin D Deficiency in African Children
Vitamin D deficiency is a common public health problem worldwide. However, little is known about the epidemiology of vitamin D deficiency in Africa. In this thesis, I aimed to determine: 1) the prevalence of and risk factors associated with vitamin D deficiency in studies conducted in Africa; 2) the prevalence and predictors of vitamin D deficiency in African children; 3) the association between vitamin D and iron deficiency in African children; and 4) genetic variants that influence vitamin D status in Africans.
In a systematic review and meta-analyses of previous vitamin D studies in Africa, the average prevalence of low vitamin D status was 18.5%, 34.2% and 59.5% using cut-offs of 25-hydroxyvitamin D (25(OH)D) levels of <30 nmol/L, <50 nmol/L and <75 nmol/L, respectively. Populations at risk of vitamin D deficiency included newborns, women, and people living in high latitudes or urban areas.
In an epidemiological study of young children living in Africa, the prevalence of low vitamin D status was 0.6%, 7.8% and 44.5% using cut-offs of 25(OH)D levels of GC2 variant of the group-specific component (GC) gene, which encodes vitamin D binding protein.
Vitamin D deficiency was also associated with 80% higher odds of iron deficiency in these children. Adjusted regression models revealed that vitamin D deficiency was associated with higher ferritin and hepcidin levels suggesting lower iron status, and reduced sTfR and transferrin levels and increased TSAT and serum iron levels suggesting improved iron status.
Genome-wide association study (GWAS) in Africans revealed genetic variants that influence vitamin D status in vitamin D metabolism genes: DHCR7/NADSYN1, CYP2R1 and GC. However, the majority of SNPs from previous European GWASs did not replicate in the current GWAS.
Findings from this thesis indicate that vitamin D deficiency is prevalent in many African populations and should be considered in public health strategies in Africa
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
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European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.
‘Mental fight’ and ‘seeing & writing’ in Virginia Woolf and William Blake
This thesis is the first full-length study to assess the writer and publisher Virginia Woolf’s (1882-1941) responses to the radical Romantic poet-painter, and engraver, William Blake (1757-1827). I trace Woolf’s public and private, overt and subtle references to Blake in fiction, essays, notebooks, diaries, letters and drawings. I have examined volumes in Leonard and Virginia Woolf’s library that are pertinent, directly and indirectly, to Woolf’s understanding of Blake. I focus on Woolf’s key phrases about Blake: ‘Mental fight’, and ‘seeing & writing.’
I consider the other phrases Woolf uses to think about Blake in the context of these two categories. Woolf and Blake are both interested in combining visual and verbal aesthetics (‘seeing & writing’). They are both critical of their respective cultures (‘Mental fight’). Woolf mentions ‘seeing & writing’ in connection to Blake in a 1940 notebook. She engages with Blake’s ‘Mental fight’ in ‘Thoughts on Peace in an Air Raid’ (1940).
I map late nineteenth and early twentieth-century opinion on Blake and explore Woolf’s engagement with Blake in these wider contexts. I make use of the circumstantial detail of Woolf’s friendship with the great Blake collector and scholar, Geoffrey Keynes (1887-1982), brother of Bloomsbury economist John Maynard Keynes. Woolf was party to the Blake centenary celebrations courtesy of Geoffrey Keynes’s organisation of the centenary exhibition in London in 1927.
Chapter One introduces Woolf’s explicit references to Blake and examines the record of Woolf scholarship that unites Woolf and Blake. To see how her predecessors had responded, Chapter Two examines the nineteenth-century interest in Blake and Woolf’s engagement with key nineteenth-century Blakeans. Chapter Three looks at the modernist, early twentieth-century engagement with Blake, to contextualise Woolf’s position on Blake. Chapter Four assesses how Woolf and Blake use ‘Mental fight’ to oppose warmongering and fascist politics. Chapter Five is about what Woolf and Blake write and think about the country and the city. Chapter Six discusses Woolf’s reading of John Milton (1608-1674) in relation to her interest in Blake, drawing on the evidence of Blake’s intense reading of Milton. Chapter Seven examines further miscellaneous continuities between Woolf and Blake. Chapter Eight proposes, in conclusion, that we can only form an impression of Woolf’s Blake.
The thesis also has three appendices. First, a chronology of key publications which chart Blake’s reputation as well as Woolf’s allusions to Blake. Second a list all of Blake’s poetry represented in Woolf’s library including contents page. The third lists all the other volumes in Woolf’s library that proved relevant. Although Woolf’s writing is the subject of this thesis, my project necessitates an attempt to recover how Blake was understood and misunderstood by numerous writers in the early twentieth century. The thesis argues Blake is a model radical Romantic who combines the visual and the verbal and that Woolf sees him as a kindred artist
The Metabolic Impact of Two Different Parenteral Nutrition Lipid Emulsions in Children after Hematopoietic Stem Cell Transplantation: A Lipidomics Investigation
This research was funded by the "Salud Investiga Modalidad Joven 2010" award from the Junta de Andalucia, Spain and CIBERobn.Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow
or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the
clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during
HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma
and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic
soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry
platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant
chemical subclasses affected. In addition, we explored the interrelation between the lipidomics
profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers
of inflammation, and antioxidant defense using an innovative data integration analysis based on
Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several
lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines
(PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE),
oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not.
Several connections across the different blocks of data were found and aid in interpreting the impact
of the lipid emulsions on metabolic health.Junta de Andalucia
European CommissionCIBERob
Um modelo para suporte automatizado ao reconhecimento, extração, personalização e reconstrução de gráficos estáticos
Data charts are widely used in our daily lives, being present in regular media,
such as newspapers, magazines, web pages, books, and many others. A well constructed
data chart leads to an intuitive understanding of its underlying data
and in the same way, when data charts have wrong design choices, a redesign
of these representations might be needed. However, in most cases, these
charts are shown as a static image, which means that the original data are not
usually available. Therefore, automatic methods could be applied to extract the
underlying data from the chart images to allow these changes. The task of
recognizing charts and extracting data from them is complex, largely due to the
variety of chart types and their visual characteristics.
Computer Vision techniques for image classification and object detection are
widely used for the problem of recognizing charts, but only in images without
any disturbance. Other features in real-world images that can make this task
difficult are not present in most literature works, like photo distortions, noise,
alignment, etc. Two computer vision techniques that can assist this task and
have been little explored in this context are perspective detection and
correction. These methods transform a distorted and noisy chart in a clear
chart, with its type ready for data extraction or other uses. The task of
reconstructing data is straightforward, as long the data is available the
visualization can be reconstructed, but the scenario of reconstructing it on the
same context is complex.
Using a Visualization Grammar for this scenario is a key component, as these
grammars usually have extensions for interaction, chart layers, and multiple
views without requiring extra development effort.
This work presents a model for automated support for custom recognition, and
reconstruction of charts in images. The model automatically performs the
process steps, such as reverse engineering, turning a static chart back into its
data table for later reconstruction, while allowing the user to make modifications
in case of uncertainties. This work also features a model-based architecture
along with prototypes for various use cases. Validation is performed step by
step, with methods inspired by the literature. This work features three use
cases providing proof of concept and validation of the model.
The first use case features usage of chart recognition methods focused on
documents in the real-world, the second use case focus on vocalization of
charts, using a visualization grammar to reconstruct a chart in audio format,
and the third use case presents an Augmented Reality application that
recognizes and reconstructs charts in the same context (a piece of paper)
overlaying the new chart and interaction widgets. The results showed that with
slight changes, chart recognition and reconstruction methods are now ready for
real-world charts, when taking time, accuracy and precision into consideration.Os gráficos de dados são amplamente utilizados na nossa vida diária, estando
presentes nos meios de comunicação regulares, tais como jornais, revistas,
páginas web, livros, e muitos outros. Um gráfico bem construído leva a uma
compreensão intuitiva dos seus dados inerentes e da mesma forma, quando
os gráficos de dados têm escolhas de conceção erradas, poderá ser
necessário um redesenho destas representações. Contudo, na maioria dos
casos, estes gráficos são mostrados como uma imagem estática, o que
significa que os dados originais não estão normalmente disponíveis. Portanto,
poderiam ser aplicados métodos automáticos para extrair os dados inerentes
das imagens dos gráficos, a fim de permitir estas alterações. A tarefa de
reconhecer os gráficos e extrair dados dos mesmos é complexa, em grande
parte devido à variedade de tipos de gráficos e às suas características visuais.
As técnicas de Visão Computacional para classificação de imagens e deteção
de objetos são amplamente utilizadas para o problema de reconhecimento de
gráficos, mas apenas em imagens sem qualquer ruído. Outras características
das imagens do mundo real que podem dificultar esta tarefa não estão
presentes na maioria das obras literárias, como distorções fotográficas, ruído,
alinhamento, etc. Duas técnicas de visão computacional que podem ajudar
nesta tarefa e que têm sido pouco exploradas neste contexto são a deteção e
correção da perspetiva. Estes métodos transformam um gráfico distorcido e
ruidoso em um gráfico limpo, com o seu tipo pronto para extração de dados
ou outras utilizações. A tarefa de reconstrução de dados é simples, desde que
os dados estejam disponíveis a visualização pode ser reconstruída, mas o
cenário de reconstrução no mesmo contexto é complexo.
A utilização de uma Gramática de Visualização para este cenário é um
componente chave, uma vez que estas gramáticas têm normalmente
extensões para interação, camadas de gráficos, e visões múltiplas sem exigir
um esforço extra de desenvolvimento.
Este trabalho apresenta um modelo de suporte automatizado para o
reconhecimento personalizado, e reconstrução de gráficos em imagens
estáticas. O modelo executa automaticamente as etapas do processo, tais
como engenharia inversa, transformando um gráfico estático novamente na
sua tabela de dados para posterior reconstrução, ao mesmo tempo que
permite ao utilizador fazer modificações em caso de incertezas. Este trabalho
também apresenta uma arquitetura baseada em modelos, juntamente com
protótipos para vários casos de utilização. A validação é efetuada passo a
passo, com métodos inspirados na literatura. Este trabalho apresenta três
casos de uso, fornecendo prova de conceito e validação do modelo.
O primeiro caso de uso apresenta a utilização de métodos de reconhecimento
de gráficos focando em documentos no mundo real, o segundo caso de uso
centra-se na vocalização de gráficos, utilizando uma gramática de visualização
para reconstruir um gráfico em formato áudio, e o terceiro caso de uso
apresenta uma aplicação de Realidade Aumentada que reconhece e reconstrói
gráficos no mesmo contexto (um pedaço de papel) sobrepondo os novos
gráficos e widgets de interação. Os resultados mostraram que com pequenas
alterações, os métodos de reconhecimento e reconstrução dos gráficos estão
agora prontos para os gráficos do mundo real, tendo em consideração o
tempo, a acurácia e a precisão.Programa Doutoral em Engenharia Informátic
Development of in-vitro in-silico technologies for modelling and analysis of haematological malignancies
Worldwide, haematological malignancies are responsible for roughly 6% of all the cancer-related deaths. Leukaemias are one of the most severe types of cancer, as only about 40% of the patients have an overall survival of 10 years or more. Myelodysplastic Syndrome (MDS), a pre-leukaemic condition, is a blood disorder characterized by the presence of dysplastic, irregular, immature cells, or blasts, in the peripheral blood (PB) and in the bone marrow (BM), as well as multi-lineage cytopenias.
We have created a detailed, lineage-specific, high-fidelity in-silico erythroid model that incorporates known biological stimuli (cytokines and hormones) and a competing diseased haematopoietic population, correctly capturing crucial biological checkpoints (EPO-dependent CFU-E differentiation) and replicating the in-vivo erythroid differentiation dynamics. In parallel, we have also proposed a long-term, cytokine-free 3D cell culture system for primary MDS cells, which was firstly optimized using easily-accessible healthy controls. This system enabled long-term (24-day) maintenance in culture with high (>75%) cell viability, promoting spontaneous expansion of erythroid phenotypes (CD71+/CD235a+) without the addition of any exogenous cytokines. Lastly, we have proposed a novel in-vitro in-silico framework using GC-MS metabolomics for the metabolic profiling of BM and PB plasma, aiming not only to discretize between haematological conditions but also to sub-classify MDS patients, potentially based on candidate biomarkers. Unsupervised multivariate statistical analysis showed clear intra- and inter-disease separation of samples of 5 distinct haematological malignancies, demonstrating the potential of this approach for disease characterization.
The work herein presented paves the way for the development of in-vitro in-silico technologies to better, characterize, diagnose, model and target haematological malignancies such as MDS and AML.Open Acces
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