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M.S.

There currently does not exist a way for creating digital twins’information and transferring it between networks , but container-basedvirtualization could be a possible solution. One of those techniques isDocker, which is an engine to isolate a software and can bring benefits toimprove the workflow of software development. Making changes withDocker is very fast as it uses the copy-on-write model, it can containerizeapplications in minutes. This study will design a scenario with twodevices sending a data packet between each other to simulate theproblem. The results from the study is further investigate and analyze toanswer the question of whether the container-based virtualization can bea possible solution for creating digital twins. The result from the scenariois Docker works equal or worse when used with a low-cost computinghardware compared to a computing hardware. It is speculated that theresources used in the images is a factor that can affect the performance,but the hardware is also another factor that can affect it. / Det finns för närvarande inget sätt att skapa digitala tvillingar ochöverföra den mellan nätverk, men containerbaserad virtualisering kanvara en möjlig lösning. En av containerbaserad virtualisering tekniker ärDocker, som är en motor för att isolera en programvara och kanframbringa fördelar för att förbättra arbetsflödet för programutveckling.Att göra ändringar med Docker är mycket snabbt tack vare användningav copy-on-write-modellen. Denna studie kommer att utforma ettscenario med två enheter som skickar ett datapaket mellan varandra fratt simulera överföringsprocessen. Mätresultat från studien bliranalyserad för att besvara frågan om containerbaserad virtualisering kanvara en möjlig lösning för att skapa och skicka digitala tvillingar.Resultatet från scenariot är att Docker fungerar lika eller sämre när detanvänds med en låg kostnad datorhårdvara jämfört med endatorhårdvara. Det spekuleras att resurserna som används i datapaketetär en faktor som kan påverka prestandan, men hårdvaran är också enannan faktor som påverkar det.

We developed a pipeline to identify the copy number polymorphisms (CNPs) in the Northern Swedish population using whole genome sequencing (WGS) data. Two different methodologies were applied to discover CNPs in more than 1,000 individuals. We also studied the association between the identified CNPs with the expression level of 438 plasma proteins collected in the same population. The identified CNPs were summarized and filtered as a population copy number matrix for 1,021 individuals in 243,987 non-overlapping CNP loci. For the 872 individuals with both WGS and plasma protein biomarkers data, we conducted linear regression analyses with age and sex as covariance. From the analyses, we detected 382 CNP loci, clustered in 30 collapsed copy number variable regions (CNVRs) that were significantly associated with the levels of 17 plasma protein biomarkers (p < 4.68×10-10).

La production verbale écrite constitue un vaste champ d’investigation pour les sciences cognitives. A l’heure où il est demandé de plus en plus tôt de savoir produire avec les outils numériques de production verbale écrite (clavier d’ordinateur et tablette tactile), l’utilisation de ces outils nécessite d’être étudiée. Nous proposons d’examiner les effets de trois outils sur la production (stylo numérique, clavier et tablette tactile). Pour ce faire, nous avons réalisé quatre études : la première porte sur la production orthographique en condition de dictée ; la deuxième s’intéresse à la copie de mots ; la troisième concerne la reproduction de phrases ; la quatrième aborde la production de textes.Nos analyses montrent que la variable outil de production a une grande importance lors de la production verbale écrite de mots, de phrases ainsi que sur la production de textes. Nous avons pu mettre en évidence l’effet de ces outils sur les temps de production, le nombre d’erreurs, la récupération d’information, le débit et la qualité des textes produits. Nos recherches ouvrent des perspectives nouvelles tant sur le plan méthodologique que sur le plan théorique. En effet, l’outil de production est une variable qu’il faut prendre en compte dans l’étude de la production verbale écrite. / Written verbal production is a vast field of investigation for cognitive sciences. At a time when it is asked at an increasingly early age to know how to produce with the digital tools of written verbal production (computer keyboard and touch tablet), the use of these tools needs to be studied. We propose to examine the effects of three tools on production (digital pen, keyboard and touch pad). To do so, we conducted four studies: the first deals with orthographic production in dictation condition; the second is about copying words; the third concerns the reproduction of sentences; the fourth deals with the production of texts.Our analyzes show that the variable production tool is of great importance in the verbal production of words, phrases and the production of texts. We have been able to highlight an effect of these tools on production times, the number of errors, the retrieval of information, the throughput and the quality of the texts produced. Our research opens up new perspectives both from a methodological and a theoretical point of view. Indeed, the tool of production is a variable that must be taken into account in the study of written verbal production.

Mestrado em Ciências Forenses / Master Degree Course in Forensic Sciences / A possibilidade de analisar amostras com quantidades exíguas de material genético (amostras Low Copy Number ou LCN), em que estão presentes apenas algumas células, tem alterado a forma de encarar a cena do crime. Alguns vestígios que até agora não eram considerados como susceptíveis de proporcionarem resultados, podem actualmente ser analisados com sucesso. As impressões digitais são um bom exemplo. Estes vestígios apresentam um baixo número de células, permitindo apenas recuperar quantidades de DNA inferiores a 100 pg. Assim, para a análise do DNA nuclear, é necessário implementar sistemas muito sensíveis que consistem, habitualmente, no aumento do número de ciclos da PCR. Contudo, alguns artefactos são produzidos, tornando difícil a interpretação dos electroforectogramas. Neste trabalho pretendeu-se comparar a aplicação do estudo de STR autossómicos, Y-STR e miniSTR na análise genética de impressões digitais, partindo do conceito do aumento do número de ciclos como estratégia para se obter maior sensibilidade. Procedeu-se também à amplificação total do genoma e nested-PCR, como métodos alternativos ao aumento do número de ciclos. Adicionalemente, neste estudo tentou-se perceber a influência dos principais métodos reveladores de impressões digitais (cianoacrilato, pó magnético e pó branco) na análise do DNA. Os resultados mostram que o aumento do número de ciclos é a melhor opção como método para aumentar a sensibilidade. Constata-se também que o DNA extraído de impressões digitais encontra-se parcialmente degradado, obtendo-se diferenças significativas entre loci com fragmentos de amplificação menores e maiores do que 200 pb. Dos diferentes marcadores caracterizados verifica-se que, em termos de percentagem de alelos detectados, os miniSTR proporcionam os melhores resultados. Por outro lado, os Y-STR parecem altamente sensíveis à degradação ou presença de inibidores, pelo que são menos robustos para este tipo de análises. Verifica-se também que os perfis LCN são drasticamente afectados por artefactos, principalmente os derivados de variação estocástica, como o allele dropout e o desequilíbrio heterozigótico. A determinação de perfis de consenso permite reduzir alguns destes artefactos. Dos métodos de revelação estudados, o cianoacrilato é o que apresenta menor influência na análise e, pelo contrário, o pó branco provoca os resultados mais negativos. / The possibility to perform low copy number DNA typing, when just a few cells are available, as changed the way how crime scene investigations is faced. Nowadays it is possible to successfully type some evidence that couldn t be considered until now. Fingerprints are a good example of those. Since that just a few cells are present in this evidence (enabling recovery of low quantities of DNA, fewer than 100pg) just very sensitive systems can detect nuclear DNA. The most used method is definitely increasing the number of PCR cycles. However, increased occurrence of stutters and artifacts that reduced the quality of the DNA profile is normally observed. The present work aimed to compare the application of autosomic STR, Y-STR and miniSTR markers, based on the concept of increased number of PCR cycles as a strategy to achieve more sensitivity. Some other methods, such as whole genome amplification and nested-PCR, were also evaluated as an alternative way to reach the desired sensitivity. Another goal was to determine the influence of several reagents for developing latent fingerprints (cyanoacrylate fuming, magnetic powder and white powder) in DNA typing. The results shows that increasing the number of PCR cycles still is the best way to attain the required sensitivity. Moreover we could realize that DNA was partially degraded, once there were observed significant differences between loci larger and smaller than 200bp. Among all markers miniSTR showed to perform the best results in terms of detected alleles percentage. On the other hand, Y-STR seemed to be highly affected in the presence of degraded DNA and PCR inhibitors, which makes them less robust for these analyses. LCN profiles are significantly affected by artifacts, like allele dropout and heterozygous imbalance, derived from stochastic fluctuation. Reporting consensus profiles reduces artifact inherent errors. Finally, cyanoacrylate proved to have a minimum negative effect on DNA profiling, while white powder was the worst reagent.

The transcription in the eukaryotic cells involves epigenetic regulatory mechanisms that control local and higher-order chromatin remodelling. In the skin, keratinocyte-specific genes are organized into distinct loci including Epidermal Differentiation Complex (EDC) and Keratin type I/II loci. This thesis introduces bioinformatics approaches to analyze multi-level regulatory mechanisms that control skin development and keratinocyte-specific differentiation. Firstly, integration of gene expression data with analyses of linear genome organization showed dramatic downregulation of the genes that comprise large genomic domains in the sweat glands including EDC locus, compared to ii hair follicles, suggesting substantial differences in global genome rearrangement during development of these two distinct skin appendages. Secondly, comparative analysis of the genetic programmes regulated in keratinocytes by Lhx2 transcription factor and chromatin remodeler Satb1 revealed that significant number of their target genes is clustered in the genome. Furthermore, it was shown in this study that Satb1 target genes are lineage-specific. Thirdly, analysis of the topological interactomes of Loricrin and Keratin 5 in hair follicle steam cells revealed presence of the cis- and trans-interactions and lineage specific genes (Wnt, TGF-beta/activin, Notch, etc.). Expression levels of the genes that comprise interactomes show correlation with their histone modification status. This study demonstrates the crucial role for integration of transcription factormediated and epigenetic regulatory mechanisms in establishing a proper balance of gene expression in keratinocytes during development and differentiation into distinct cell lineages and provides an integrated bioinformatics platform for further analyses of the changes in global organization of keratinocyte-specific genomic loci in normal and diseased skin.

The transcription in the eukaryotic cells involves epigenetic regulatory mechanisms that control local and higher-order chromatin remodelling. In the skin, keratinocyte-specific genes are organized into distinct loci including Epidermal Differentiation Complex (EDC) and Keratin type I/II loci. This thesis introduces bioinformatics approaches to analyze multi-level regulatory mechanisms that control skin development and keratinocyte-specific differentiation. Firstly, integration of gene expression data with analyses of linear genome organization showed dramatic downregulation of the genes that comprise large genomic domains in the sweat glands including EDC locus, compared to ii hair follicles, suggesting substantial differences in global genome rearrangement during development of these two distinct skin appendages. Secondly, comparative analysis of the genetic programmes regulated in keratinocytes by Lhx2 transcription factor and chromatin remodeler Satb1 revealed that significant number of their target genes is clustered in the genome. Furthermore, it was shown in this study that Satb1 target genes are lineage-specific. Thirdly, analysis of the topological interactomes of Loricrin and Keratin 5 in hair follicle steam cells revealed presence of the cis- and trans-interactions and lineage specific genes (Wnt, TGF-beta/activin, Notch, etc.). Expression levels of the genes that comprise interactomes show correlation with their histone modification status. This study demonstrates the crucial role for integration of transcription factormediated and epigenetic regulatory mechanisms in establishing a proper balance of gene expression in keratinocytes during development and differentiation into distinct cell lineages and provides an integrated bioinformatics platform for further analyses of the changes in global organization of keratinocyte-specific genomic loci in normal and diseased skin.

BACKGROUND:14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro.METHODS:qRTPCR and Western blot analysis were performed to examine 14-3-3gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3gamma promoter.RESULTS:Quantitative rtPCR results showed that the expression level of 14-3-3gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3gamma expression.CONCLUSION:Increased expression of 14-3-3gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.