5 Abstract Aims Determination of gene expression of HBG1 gamma globin in myelodysplastic syndrome (MDS) patients in CD34+ pluripotent hæmatopoietic cells and connection of HBG1 gene expression with various subtypes of MDS. Furthermore, detection of single nucleotide polymorphisms rs 4671393 and rs 11886868 in these patients and in healthy Czech population donors and to determine whether a connection exists between the occurrence of the above polymorphisms and HBG1 gene over-expression, as demonstrated in some hæmatological disorders. Samples The source of genetic material to identify gene expression were 80 HBG1 RNA samples isolated from the pluripotent hematopoietic CD34+ cells of MDS patients. As a sample of healthy controls, 6 samples of commercially purchased CD 34+ cells from the Lonza com- pany were used. The source of genetic material for the detection of polymorphisms were 140 DNA samples isolated from purified granulocytes of MDS patients and 49 samples of DNA isolated from peripheral blood granulocytes from healthy Czech population donors. Methods Real-Time PCR was used to determine HBG1 gene expression and detection of single nu- cleotide polymorphisms. Taqman Gene Expression Assay was used to determine the level of expression and the results were evaluated using the comparative ΔΔCT method....

Šiame magistro darbe aptarsime keletą projekcijos metodų: tai pagrindinių komponenčių analizė (Principal Component Analysis (PCA)), daugiamačių skalių (Multidimensional Scaling (MDS)) ir santykinės perspektyvos (relational perspective map (RPM)). Tirsime, kuris iš trijų pradinių projekcijos taškų parinkimo būdų - atsitiktinis, pagrindinių komponenčių ar didžiausių dispersijų garantuoja mažesnę paklaidą RPM algoritme. Atliksime paprasto RPM algoritmo, pasiūlyto autoriaus James Xinzhi Li modifikaciją. Taip pat tirsime parametrus r,a (mokymo greičiai), nustatysime, kaip jie įtakoja RPM algoritmo konvergavimą. Integruosime MDS ir RPM algoritmus į internetinę terpę. Vizualiai vaizduosime daugiamačių duomenų projekcijas. / This paper deals with a methods, called the relational perspective map and multidimentional scaling. Relational perspective map that visualizes multidimensional data onto two-dimensional closed plane. It tries to preserve the distances between the multidimensional data in the lowerdimensional space. But the most important feature of the relational perspective map is the ability to visualize data in a non-overlapping manner so that it reveals small distances better than other known visualization methods. In the methods are In this paper, the features of relational perspective map are explored experimentally and some disadvantages are noticed. We have proposed a modification of this method, which enables us to avoid them. Also we have stored RPM and MDS algorithms in php language and included them in web site for testing these methods online. But allow testing only small data, because algorithms in php language works longer that stored in c++ language.

Submitted by Amanda Silva (amanda.osilva2@ufpe.br) on 2015-03-05T14:59:36Z No. of bitstreams: 2 DISSERTAÇÃO Gilberto de Freitas.pdf: 4900249 bytes, checksum: 0091d84b4ab151d123911a03867fac40 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-05T14:59:36Z (GMT). No. of bitstreams: 2 DISSERTAÇÃO Gilberto de Freitas.pdf: 4900249 bytes, checksum: 0091d84b4ab151d123911a03867fac40 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2014-02-19 / As informações e características com respeito ao relevo são de fundamental importância para o planejamento e a execução de obras de engenharia. Atualmente, além do método convencional de obtenção de dados altimétricos através de levantamento topográfico, existem novos métodos e tecnologias para obtenção desses dados dentre os quais se destaca a estereoscopia de imagens orbitais, a interferometria SAR (Radar de Abertura Sintética) e o perfilamento a laser. Considerando a facilidade de aquisição de várias fontes de informações altimétricas que são disponibilizadas na internet, a qualidade altimétrica dos MDSs obtidos a partir de sensores orbitais tem recebido importante destaque. Pesquisas têm sido direcionadas no desenvolvimento de metodologias para a geração e validação de dados altimétricos de diferentes sensores. Dessa forma, a presente pesquisa apresenta a análise comparativa da qualidade posicional altimétrica dos modelos SRTM, ASTER GDEM e TOPODATA, utilizando diferentes tipos de amostragem e a aplicação de simulação com diferentes tamanhos amostrais, tendo como referencia dados de maior precisão, obtidos através de aerofotogrametria e levantamento via GNSS. Todo o trabalho levou em conta o Padrão de Exatidão Cartográfica dos Produtos Cartográficos Digitais (PEC-PCD), definido na nova norma de qualidade, considerando a abordagem proposta pela CONCAR (2011) no Brasil.

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近年來資料產生的數量遠超過過去可處理的數量，以現今的個人電腦使用傳統的方法已經無法處理大資料的運算與分析，所以改善傳統的方法與平行化為必經的方向，本論文以拆解合成-多元尺度法的平行化為主要討論對象，除了介紹Python程式語言及其相關套件如何撰寫平行化程式，我們將拆解合成-多元尺度法從原本的單核心版本改進為多核心版本，並且探索拆解合成-多元尺度法在平行化過程中的計算效能，藉以了解拆解合成-多元尺度法在平行化計算時的參數要如何設定，使得平行化的SC-MDS可以有最高的計算效率。經實驗證明多核心底下的SC-MDS平行化又把SC-MDS單核心的效能做個再次的提升。 / In recent years, the number of generated data is growing fast such that it is infeasible to process by using traditional methods. So improving traditional methods and developing paralled computing methods are important issues. The main contribution of this thesis is to delelope the parallel version of the split-and-combine multidimensional scaling method(SC-MDS). We will fistly introduce fundamental python program, the basic python packages and the python multi-core program. Then we will implement the serial core version of SC-MDS to the multi-core version. Moreover, we will discover the efficiency of the multi-core version of SC-MDS. Then we can understand how to determine the parameters of the parllel version of SC-MDS. By our experimental results, we successfully implement the serial core of SC-MDS to the faster parallel version of SC-MDS.

The James Lind Alliance approach is a widely used method for research priority setting, yet comprehensive reviews of its implementation are lacking. This thesis therefore focused on reviewing and analyzing the barriers and facilitators to its implementation and on carrying out the early stages of our own priority setting partnership to prioritize research in myelodysplastic syndromes (MDS). A scoping review of the barriers and facilitators encountered when undertaking a James Lind Alliance priority setting partnership was conducted. Our analysis identified that most barriers could be categorized into three main areas: representation, data collection and processing and result useability. We also identified a number of methods that were used successfully to overcome some of the barriers and offered our suggestions for further study. Along with the Aplastic Anemia and Myelodysplasia Association of Canada, we conducted the initial stages of the Canadian MDS Priority Setting Partnership. We were able to collect 206 relevant research questions from people living with MDS, their caregivers and front line health professionals which can be put forward for further prioritization.

The identification and understanding of early drivers in malignancy is crucial to revert preleukemic events and prevent leukemic relapse. Del(20q) is one of the most common primary cytogenetic abnormalities found in preleukemic malignancies from myeloproliferative neoplasms to myelodysplastic syndrome (MDS). Previous studies have identified a “common retained region” within 20q11.21 that is often amplified in a subset of MDS patients. PLAGL2 is one of the 4 genes identified to be within the minimally conserved amplified region. Indeed, in previously published datasets of MDS hematopoietic stem and progenitor cells (HSPCs) transcriptome, PLAGL2 is significantly elevated in del(20q) patients compared to healthy controls. However, we have found that its level is also higher in HSPCs of cytogenetically normal MDS patients with low blasts. Given these findings, we sought to define the role of PLAGL2 as a potential early driver of myeloid malignancies. Results In healthy cord blood (CB) HSPCs, PLAGL2 overexpression enhanced proliferation ex vivo, better maintained stemness and decreased apoptosis. Colony formation assays also identified increased output of the erythroid lineage. Xenotransplanted CB CD34+ HSPCs overexpressing PLAGL2 exhibited increased engraftment competitiveness and led to splenomegaly with signs of hypercellularity after 20 weeks, features consistent with clinical observations of hematological malignancy. Grafts derived from PLAGL2 overexpressing cells reproducibly maintained a significantly larger CD34+ HSPC compartment. Intriguingly we also identified that ~50% of PLAGL2-overexpressing grafts exhibited a significant erythroid (CD71+/CD235a+) component where none was observed in the control group. This unique finding of aberrant erythropoiesis is reminiscent of clinical observations in patients with 20q11.21 amplification, where a high proportion of erythroblasts in the marrow and in some cases progression to erythroleukemia was noted. To evaluate the progression of PLAGL2-overexpressing grafts, further secondary transplantations were carried out and showed the persistence of only immature erythroid progenitors (CD71+/CD235a-) coupled with a near complete absence of lymphopoiesis in the same grafts. Together, our data strongly suggests ectopic levels of PLAGL2 can independently drive the expansion of human HSPCs and enforce features of myeloid malignancy. To uncover the molecular mechanism underlying PLAGL2 function, we performed RNA-seq and CUT&RUN in human CB CD34+ HSPCs overexpressing PLAGL2. Gene set enrichment analysis of the transcriptome and over-representation analysis of bound genes both identified signatures consistent with LSCs. We compared these findings with identically-derived omics profiles of HSPCs overexpressing PLAG1, a closely related family member that our lab has identified as a potent expander of HSCs ex vivo but not capable of promoting malignant features. We found a strong common feature in the downregulation of ribosomal components and translation machinery, then functionally validated reduced protein synthesis in PLAGL2 overexpressing HSPCs through OP-Puro assays. We have shown dampened mRNA translation to be one of the mechanisms by which PLAG1 enhances stemness and survival of HSCs, one that potentially extends to PLAGL2 as well. However, we also identified discordant signatures, notably PLAGL2's unique capacity to reduce mitochondrial translation, a pathway associated with ineffective erythropoiesis and MDS and one potential pathway by which PLAGL2 can enforce malignant phenotypes. Finally, to investigate the potential of PLAGL2 as a therapeutic target in MDS and AML, we performed shRNA knockdown in MDSL, a human MDS cell line, and primary human AML. In vitro competitive assays with MDSL showed steady dropout of PLAGL2 depleted cells. Similarly, depletion of PLAGL2 in primary AML was also able to attenuate colony formation and engraftment in vivo, highlighting the therapeutic potential of PLAGL2 inhibition throughout myeloid malignancies. Conclusion We have identified PLAGL2's potential as an early independent driver of myeloid malignancy and aberrant erythroid differentiation. An understanding of PLAGL2 and its downstream mechanisms will not only further our understanding on the development of early myeloid malignancies but also potentially provide another avenue to treat or prevent leukemia before it manifests. / Thesis / Doctor of Philosophy (PhD)

Syftet med studien var att undersöka om och hur löneform, möjlighet till avancemang samt företagets CSR-arbete påverkar potentiella arbetssökandes intentioner att söka en ledig tjänst. Studien genomfördes på studerande vid Högskolan i Gävle. 78 personer deltog i studien och genomfördes som enkätundersökning. Resultatet analyserades med multidimensionell skalning (MDS). Det analyserade resultatet visade på två dimensioner där samtliga tre faktorer tycks påverka attraktiviteten hos en arbetsgivare. Dock verkar möjlighet till avancemang och intern karriär vara den faktor som har störst inverkan på potentiella arbetssökandes intentioner att söka en ledig tjänst. Då alla tre faktorer kan ha påverkat attraktiviteten drog vi slutsatsen att alla tre faktorerna är viktiga när det kommer till att attrahera blivande medarbetare. / The purpose of the study was to examine if and how salary, career advancements and a company´s CSR activities influence potential jobseekers intentions when it comes to applying for a job. The study was conducted among students at the University of Gävle. 78 persons participated, and the study was conducted as a survey. Multidimensional scaling (MDS) was used to analyze the result. The result showed that all three factors may have had an influence over how attractive an employer was perceived by the potential jobseekers. However according to the result, career advancements seems to have had the greatest impact when it came to influence potential jobseekers intentions to apply for a job. Although all three factors may have proven to have influence on the attractiveness of the employer, therefor is our conclusion that all three factors are crucial when it comes to attracting future employees

Cette thèse s’intéresse à deux aspects de la cryptologie symétrique liés à l’utilisation de matrices MDS dans les couches de diffusion linéaires de primitives. Une première partie se fonde sur les conceptions de couches de diffusion linéaires de schémas de chiffrement symétrique à partir de matrices MDS. Les associations entre matrices récursives, respectivement circulantes, et polynômes sont calquées pour construire de nouvelles associations entre d’autres structures de matrices et des éléments d’anneaux de polynômes non commutatifs de Ore. À l’instar des matrices récursives et circulantes, ces structures bénéficient d’implémentations matérielles légères. Des codes de Gabidulin dérivent des méthodes de construction directe de telles matrices, optimales en termes de diffusion, proches d’involutions pour l’implémentation. La seconde partie développe une attaque par différenciation de permutations dont l’architecture s’inspire de l’AES. L’utilisation d’une couche de diffusion linéaire locale avec une matrice MDS induit une description macroscopique de la propagation de valeurs de différences à travers les étapes du chiffrement. Des chemins différentiels tronqués apparaissent, qui servent de point de départ à la conception d’attaques rebond. Les travaux présentés généralisent les attaques rebond connues à l’exploitation de chemins différentiels tronqués structurés non issus d’avalanches libres. Cette structure permet de ne pas consommer tous les degrés de libertés au cours d’une seule étape algorithmique mais de les répartir en trois étapes. Une attaque sur 11 tours d’une permutation de Grostl-512 est alors déployée. / This thesis focuses on two aspects of symmetric cryptology related to the use of MDS matrices as building blocks of linear layers for symmetric primitives. A first part handles designs of linear layers for symmetric ciphers based upon MDS matrices. Associations between recursive, respectively circulant, matrices and polynomials are reproduced between other matrix structures and elements in non-commutative polynomial rings of Ore. As for recursive and circulant matrices, those structures come along with lightweight hardware implementations. From Gabidulin codes are derived direct constructions of MDS matrices with properties close to involution from hardware perspectives. The second part is about distinguishing attacks on an exemple of AES-like permutations. The use of some MDS matrix to build the linear layer induces a macroscopic description of differential trails through the different steps of the algorithm computing the permutation. Truncated differential path appears, from which rebound attack are built. Original work here generalizes rebound attack applied on permutations of GROSTL-512 from structured differential path not raised from free propagations of differences. This structure allows not to consume all degrees of freedom in a simple algorithmic step but to divide this comsumption into three algorithmic steps. An attack of a reduced-round version with 11 rounds of one permutation of GROSTL-512 can then be mounted.

O objetivo desta dissertação é realizar e comparar a aplicação da modelagem dinâmica de sistemas (MDS) e do activity based costing (ABC) para mensurar os custos em manufatura celular. Nesse sentido, foi realizada uma simulação utilizando os conceitos de MDS para obter os custos de produção de quatro produtos, em um ambiente de manufatura celular, considerando o método ABC e a comparação desses valores com a técnica de custeio tradicional ou absorção. Quanto à metodologia de pesquisa, esse trabalho é de enfoque quantitativo no qual o tipo de pesquisa é exploratório sem estabelecimento de hipóteses, porém, guiada pelos seus objetivos. Os resultados obtidos demonstram que a aplicação do ABC juntamente com a MDS é muito satisfatória quando comparada com a técnica tradicional. Finalmente, a aplicação do ABC com a MDS pode ser utilizada eficientemente como um método alternativo para custeio em manufaturas celulares. / The aim of this dissertation is to apply and to compare the modeling system dynamics (MDS) and activity based costing (ABC) to measure the costs in cellular manufacture. Taking this into account, a simulation was accomplished using the concepts of MDS to obtain the costs of production of four products, in an environment of cellular manufacture, considering ABC method and the comparison of those values with the technique of traditional costing. As for the research methodology, this dissertation is of quantitative focus in which the research type is exploratory without establishment of hypotheses, however guided by their objectives. The obtained results demonstrate that the application of ABC together with MDS it is very satisfactory when compared with the traditional technique. In conclusion, it can be observed that the application of ABC with MDS can be used efficiently as an alternative method to costing in cellular manufacture.