Cílem této diplomové práce je vytvoření reálného projektu s pomocí využití dvou softwarových produktů a jejich následné porovnání za použití metod vícekriteriálního hodnocení variant. Prvním softwarovým produktem je Microsoft Project. Tato aplikace je přímo určena pro plánování a řízení projektů a pro komunikaci s projektovým týmem. Druhým produktem je aplikace Microsoft Dynamics AX a v ní modul Projekt. Modul je určen pro řízení projektů, správu zdrojů, vytváření odhadů a prognóz, sledování rozpočtů a reálných výdajů na konkrétní projekt či časové plánování. Aplikace MS Dynamics AX je řešením pro plánování a řízení firemních zdrojů (ERP) a e-business, stejně tak i pro řízení vztahů se zákazníky, řízení výroby, řízení dodavatelského řetězce, fungování elektronického obchodu nebo finančního řízení.

Cílem diplomové práce je aplikace modelů vícekriteriálního rozhodování na reálný rozhodovací problém ve firmě INVEST TEL AUTO s.r.o. V praktické části je pomocí několika metod vícekriteriálního hodnocení variant nejprve vybrána nejvhodnější automobilová značka, poté je pomocí metod spojitého vícekriteriálního rozhodování navržena skladba první objednávky vozů vybrané automobilové značky.

The work describes the situation regarding the reconstruction of buildings on the Budovateľská street in Prešov and the creation of alternative options and possibilities for realization of the rebuilding. The best variant is chosen, based on the multicriterion evaluation of the variants, which was a main point of the work. For the winning variant a business plan was developed, including project schedule, analysis of financing, market and competition research, as well as pricing and marketing strategy. An important part of the plan was the financial plan, in which financial statements, such as balance sheet, income statement and cash flow statement were created. Another significant part was the risk analysis and the evaluation of the project by quantitative financial indicators.

The aim of this thesis is to find suitable mortgage, describe important criteria for comparison of mortgages and what types of mortgages the banks offer. The theoretical part of the thesis is divided into four parts. At first, I describe methods of determining the weights and methods of multi-criteria decision making. Then I focus on information about mortgage loan and about loan application process. In the third part I present variants and criteria and in the fourth I detect the best mortgage. I used WSA, TOPSIS, ELECTRE III and MAPPAC and add-on of Microsoft Excel - Sanna.

The aim of the work is the selection of individuals or groups of employees using the methods multicriteria evaluation of alternatives. First outline the issue of human resources and focusing specifically on the acquisition, selection and recruitment of employees. Then we move on the theory of decision making, testing of non-dominated solution and calculation of the Saaty's weights. We will describe in detail the methods: ORESTE, WSA, TOPSIS, ELECTRE I, ELECTRE III and Cook-Seiford method for the selection of the expert team. In other parts of the work of the above findings apply to a particular fictional example, carry out a comparison of the methods for the multicriteria evaluation of the alternatives and choose group of 10 candidates, to which we will use the group expert choice for group selection. At the conclusion we summarize the work and we determine the winning candidate or the winning group.

O presente estudo tem por objetivo registrar a variação dialetal no léxico do município de Guiratinga-MT. Para isto utilizou-se do Questionário Semântico-Lexical do projeto ALiB, versão 2001, na recolha in loco do corpus, a qual se deu em conformidade com os princípios metodológicos da Geolinguística atual, em três pontos do município: a sede e dois distritos.Na sede foram entrevistados 05 homens e 05 mulheres em cada uma das quatro faixas etárias estabelecidas: acima de 65 anos, 50/64 anos, 35/49 anos e 20/34 anos; no distrito 1, Alcantilado, entrevistaram-se 02 homens e 02 mulheres em cada faixa etária; no distrito 2, Vale Rico, os sujeitos entrevistados foram 03 homens e 03 mulheres, também naquelas faixas etárias. Os dados obtidos a partir dessas respostas estão em tabelas nas quais consideram ponto linguístico, faixa etária, gênero e frequência absoluta e relativa de acordo com as noções de estatística lexical de Muller. Ao final de cada área semântica expõem-se as lexias mais frequentes em histogramas, e a seguir se dão as análises, privilegiando a abordagem semântico-lexical, com base em Rastier semas inerentes e aferentes , a partir da concepção de norma de Coseriu. Enfim, a pesquisa apresenta a realidade linguística de um pequeno município do centro-oeste do Brasil, antes que ela se perca pela ação natural de dinâmica e mutabilidade da própria língua ou por questões denominadas homogeneizadoras. / The present study has as aim to register the lexical dialectal variation of Guiratinga-MT; In order to reach that objective, the Semantics-Lexical Questionnaire, of the ALiB project, version 2001, was used during the collection of corpus in loco, according to the current Geolinguistics methodological principles, in three sites: the headquarter (the town) and two districts. In the headquarter, 5 men and 5 women from each of the following age categories were interviewed: over 65 years old, 50/64 years old, 35/49 years old and 20/34 years old; in the first district, Alcantilado, 2 men and 2 women of those age categories were interviewed. The obtained data are in tables which consider linguistics point, age, gender, and, absolute and relative frequency, in accordance to Mullers lexical statistics notion. At the end of each semantical field, the most frequent lexis were exposed in histograms, followed by analysis, granting the semantical lexical approach, based on Rastier inherent and afferent semas from the model conception of Coseriu. Finally, the study presents the linguistics reality of a small town in the Brazilian Midwest, before it disappears because of the natural action of dynamics and changeability of the own language, or because of homogenizing matters.

The Apprentices' Tower of Hanoi is introduced in this thesis. Several bounds are found in regards to optimal algorithms which solve the puzzle. Graph theoretic properties of the associated state graphs are explored. A brief summary of other Tower of Hanoi variants is also presented.

Clefts of the lip and/or palate (CL/P) are one of the most common birth defects in the world occurring about every 1 in 700 live births. Individuals with non-syndromic clefting (NSCL/P) account for about 70% of all cleft cases and exhibit a cleft only whereas syndromic occurrences (SCL/P) include additional cognitive or structural abnormalities. Linkage, genome-wide association, candidate gene, animal model, sequencing and copy number variant (CNV) analyses have been used to study CL/P and have established that it is a heterogeneous, complex disorder. However, the impact of identified sequence variants on protein structure and the contribution of structural genetic variation to CL/P remains poorly understood. In our first analysis we reassessed the phenotype of a 30-year-old individual of SCL/P and noticed phenotypic overlap with Hartsfield syndrome, a rare syndrome resulting from sequence variants in Fibroblast growth factor 1 (FGFR1). We sequenced the coding region of FGFR1 and identified a novel, de novo variant. Due to the fact sequence variants in FGFR1 contribute to multiple syndromes encompassing a wide phenotypic spectrum, we performed an extensive literature search to record every published sequence variant of FGFR1 and mapped it to the protein structure by disease and phenotype. Although no statistically significant protein domain-phenotype correlations were identified, many regions neared significance. This work stresses the need for systematic, comprehensive phenotyping of patients and provides a method for assessing the impact of the location of sequence variants within the 3D structure of the protein. Although rare and common CNVs have been identified in individuals with CL/P, prior to our work no large-scale studies of rare CNVs for the identification of novel clefting genes had been performed. For our second set of analyses, we conducted two such studies, first focusing on a smaller cohort of 140 individuals with NSCL/P from the Philippines to establish our informatic and functional validation pipeline. We used whole-genome tiling arrays to assess rare deletions overlapping genes not previously implicated in clefting, and identified one deletion overlapping Isthmin1 (ISM1) and a deletion just 3’ of the gene in a second affected individual. Functional validation of Ism1 in Xenopus laevis showed strong expression in structures necessary for craniofacial development, and morpholino and CRISPR/Cas9 knockdown of Ism1 resulted in a median cleft lip in some embryos, establishing ISM1 as a novel craniofacial patterning gene. We then expanded our study and assessed genomic CNVs in 1021 individuals with NSCL/P and 81 individuals with SCL/P, finding no differences in CNV number, load or burden between these groups. We also identified 8 putative clefting genes overlapped by deletions in two or more individuals but at a rare (< 1% frequency) in the cohort. Functional validation of these genes using CRISPR/Cas9 in zebrafish and Xenopus tropicalis is currently underway. This work has identified a novel sequence variant leading to the diagnosis of Hartsfield syndrome in an individual with SCL/P, developed an innovative method for assessing the impact of sequence variation on protein structure, improved our understanding of the contribution of CNVs to SCL/P and NSCL/P and identified several putative novel clefting loci which may help explain a portion of the missing heritability of CL/P.

Orofacial clefts are a heterogeneous group of craniofacial malformations that affect the lip and/or palate and represent the most common craniofacial birth defect in humans. In 30% of patients the cleft is accompanied by additional physical or cognitive abnormalities. Hundreds of these clefting syndromes have been described, many of which have Mendelian inheritance patterns. The most common of these is Van der Woude syndrome (VWS), caused by mutations in the transcription factor IRF6 (Kondo et al. 2002). The other 70% of patients lack additional features and are considered nonsyndromic. The etiology of nonsyndromic clefts is complex and involves the combined action of multiple genetic variants interacting with environmental factors. A common approach for identifying genetic risk factor for complex disorders such as nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the genome wide association study (GWAS). We pursued a locus on 1p22 shown to be associated with NSCL/P by Beaty et al. (2010). Through a combination of expression studies in a mouse model and mutation screening in NSCL/P patients, we identified ARHGAP29 as a novel gene for NSCL/P and the likely etiologic gene at this locus. We identified eight rare variants in NSCL/P patients absent in controls including a nonsense and a frameshift mutation. These rare variants are reminiscent of previous resequencing studies that reported rare coding mutations in 20 different candidate genes for NSCL/P. We reviewed these variants and compared them with variants found in over 7000 exomes from the 1000 Genomes Project (1kGP) and NHLBI Exome Sequencing Project (ESP) to identify the variants and genes most likely to contain etiologic rare variants. We found good support for a role for rare variants in NSCL/P, particularly for MSX1 and genes of the FGF signaling pathway. We next performed several studies to understand the genetic architecture of syndromic forms of clefting, focusing on VWS and popliteal pterygium syndrome (PPS), which is allelic to VWS. We compiled all of the nearly 300 published IRF6 mutations and compared the distribution of these mutations with IRF6 variants obtained from the 1kGP and ESP exomes. We found that mutations causing VWS were significantly over-represented in the DNA-binding domain and for the most part were absent from control exomes, indicating that they are likely to be truly causative for VWS or PPS. These mutations in VWS and PPS only account for 70% of VWS and 97% of PPS. We next hypothesized that mutations in RIPK4, which causes an autosomal recessive pterygia syndrome, could underlie the remaining VWS and/or PPS cases. We found novel homozygous mutations in RIPK4 in two PPS patients. This result has significant clinical ramifications, as counseling of recurrence risk is very different for PPS patients whose disease is caused by dominant IRF6 mutations compared to recessive RIPK4 mutations. Finally, to understand the variable expressivity of VWS and PPS we performed an association study to identify genetic modifiers. We also looked for genotype-phenotype correlations between the type and location of IRF6 mutations. Although we did not find strong evidence that the candidate genes we selected from GWAS of NSCL/P or other clefting syndromes are modifiers of the VWS or PPS phenotypes, several marginal associations suggest that members of the IRF6 gene regulatory network could act as modifiers. Finally, we found evidence of a larger genotype-phenotype correlation by demonstrating that mutation-negative VWS families have a deficiency of cleft lip phenotypes. Together this work has advanced our understanding of the genetic basis of this diverse set of cleft lip and palate disorders, informing both the biology of craniofacial development and the clinical care of patients affected by these disorders.

The 16p11.2 copy-number variant (CNV) represents a well-characterized, high-risk factor for autism spectrum disorder that additionally predisposes deletion carriers (16pdel) to increased head circumference, known as macrocephaly. The 16p11.2 CNV consists of 29 known genes, many of which are associated with neurobiological processes relevant for macrocephaly such as cell proliferation and apoptosis, differentiation and cell growth. Our lab’s previous work has demonstrated that induced pluripotent stem cell (iPSC)-derived neurons from 16pdel carriers show altered cellular morphology related to growth, which include increased soma size, total dendritic length and dendritic complexity. However, specific CNV genes responsible for these phenotypes have not been established. Here, we investigate the relationship between three 16p11.2 genes and the observed cellular phenotypes. We differentiated neurons from control iPSC-derived neural progenitor cells (NPCs) and used short hairpin RNA (shRNA) to reduce the expression of these CNV genes: KCTD13, MAPK3 and C16ORF53. We then assessed neuronal morphology by evaluating soma size, total dendritic length and dendritic complexity. We demonstrate that knocking down KCTD13 and C16ORF53 increases soma size and total dendrite length, respectively, similar to that observed in 16pdel iPSC-derived neurons. For this reason, we speculate that these genes may have a role in cell growth and might underlie macrocephaly. Thus, our study investigates genes in the 16p11.2 CNV that contribute to neuronal morphology, which may have a role in influencing brain size.