Orientador: Erick da Cruz Castelli / Resumo: O complexo gênico de Antígenos Leucocitário Humanos (HLA) é a região mais variável do genoma humano. Os genes HLA de classe I são divididos em clássicos e não clássicos, a depender de suas funções primárias, níveis de expressão e polimorfismos. Assim, HLA-A, HLA-B e HLA-C são loci clássicos e estão associados à apresentação antigênica para células T citotóxicas, enquanto HLA-E, HLA-G e HLA-F são loci não clássicos e estão associados à imunomodulação e inibição de células T e NK. No entanto, o HLA-C também apresenta propriedades imunomodulatórias a partir da interação com o TCR de células T CD8 (ativação) e com receptores KIR de células NK (principalmente inibição). A maioria dos estudos sobre variabilidade dos genes HLA têm como foco suas regiões codificadoras e negligenciam regiões regulatórias – região promotora e região 3’não-traduzida (3’NT). Esta última apresenta um papel essencial na estabilidade do mRNA e no controle pós-transcricional mediado pela ligação de microRNAs (miRNA). Neste trabalho, nós avaliamos a estrutura e a variabilidade das regiões 3’NTs dos genes HLA-A, HLA-C e HLA-G por sequenciamento de nova geração além do padrão de ligação de miRNAs observado para cada gene. A região 3’NT dos genes HLA-A e HLA-C são altamente variáveis, enquanto a de HLA-G apresenta poucos pontos de variação. No entanto, os três genes apresentaram números similares de haplótipos de 3’NT frequentes. Vários miRNAs possuem potencial de regular HLA-A, HLA-C e HLA-G tanto de modo espec... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The Human Leucocyte Antigen (HLA) gene complex is the most variable region of the human genome. The class I HLA genes are classified as classical or nonclassical depending on their primary function, expression levels and polymorphism rate. Thus, HLA-A, HLA-B, and HLA-C are classical loci, associated with antigen presentation to cytotoxic T cells, while HLA-E, HLA-G, and HLA-F are non-classical loci associated with immunomodulation inhibition of both T and NK cells. Nevertheless, HLA-C also presents immumodulatory features by interacting with TCR on CD8 T (activation) cells as well as KIR receptors on NK cells (mostly inhibition). Most studies on HLA variability focus on their coding sequences and neglects their regulatory sequences – promoter and 3’untranslated region (3’UTR). The last one plays a pivotal role on mRNA stability and post-transcriptional control by microRNA (miRNA) binding. Here we evaluated 3’UTR structure and variability for HLA-A, HLA-C, and HLA-G by using massively parallel sequencing in a Brazilian population sample. We also report the miRNA binding pattern observed for each locus. Both HLA-A and HLAC 3’UTR segments are highly variable, while HLA-G 3’UTR presents few variation sites. However, the three loci present a similar number of frequent 3’UTR haplotypes. Several miRNAs are potential regulators of HLA-A, HLA-C, and HLA-G on a specific manner as well as the three of them together. This fact may be associated with the fine regulation of HLA expression ... (Complete abstract click electronic access below) / Doutor

8 ABSTRACT Author: Bc. Lucie Moravcová Supervisor: MUDr. Vít Řeháček Charles University, Faculty of Pharmacy in Hradec Králové Title of master's thesis: Kidney transplantation: donor-recipient pairing in University Hospital Hradec Králové Background: The aim of this study was to determine HLA, blood group, age and sex match in donor-recipient pairing in kidney transplantation. HLA alleles of deceased donors were typed in Transfusion Department of the University Hospital Hradec Králové. Methods: Donor's HLA-A*, HLA-B* and HLA-DRB1* alleles were typed by PCR - SSP method. Complex data evaluating and processing was then performed. Results: 97 deceased donors were tested between 2013 and 2018. A total of 98 kidneys received from them were subsequently transplanted to 98 recipients in University Hospital Hradec Králové. 60,2 % of the donors were men, 63,3 % of the recipients were men. Most of the donors, as well as the recipients, were 51-70 years old (50,0 % and 59,2 %, respectively). The most common diagnoses in the group of deceased donors were associated with brain damage (66,3 %), the most common cause of renal failure in the group of recipients was chronic inflammatory kidney disease (41,8 %). All 98 transplantations (100,0 %) were AB0 compatible. 74 transplantations (75,5 %) were RhD compatible. 5...

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Background: The major histocompatibility complex (MHC) molecules play an important role in the immune response regulation and in the maintenance of the immune homeostasis. Regulation of their expression is therefore a key factor influencing the adaptive immune response. DNA methylation of gene regulatory regions is one of the mechanisms of gene expression control that affects the accessibility of DNA to transcription factors. Ageing is connected with changes in DNA methylation and increased predisposition to autoimmune diseases in older age could be associated with changes in MHC class II genes methylation. Aims: The aim of this diploma thesis is to analyze the methylation profile of DQA1 and DQB1 genes regulatory regions and to compare its differences between the generations and between individual alleles. The next aim is to compare DQA1 mRNA expression between the generations and between single alleles. Methods: DNA and RNA were isolated from blood of three age group donors. DNA was converted by the bisulfite treatment and regulatory regions of HLA class II genes were amplified and cloned into bacteria. Positive clones were sequenced and then analyzed. RNA was reverse transcribed and its expression level was determined by real-time PCR. Results: Statistically significant differences were found by...

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Simulation provides the ability to obtain results from, and analyse, a system without physically building the system. These results can be used to inform the actual construction of the physical system, how best to use a system, how best to integrate a system with another system, and so on. A simulation can also be used to train and educate the end-users of a system either before the system is actually produced or when the availability of the actual system is limited. Most end systems are in some way composed of subsystems. The subsystems themselves may be composed of subsystems. This type of architecture is generically referred to as a system of systems. For example, a ship is composed of a hull, engines, sensors, etc. The engine system may be composed of the fuel and cooling subsystems, for example. Systems constructed this way have numerous benefits including allowing subsystems to be built independently of each other (after creating well defined interfaces), and allowing for subsystems to be replaced without affecting other subsystems. These same benefits are desirable in the construction of a simulation of a system. One simulation framework that supports these ideals is the High Level Architecture (HLA). The HLA is an international modelling and simulation framework that specifically provides for distributed simulation. The HLA uses the term federate for component simulations that are then brought together in a distributed computing environment to form a federation. The HLA defines a data model for documenting the data interfaces of the federates and the application programming interface used by the federates to communicate data. A simulation of a systems of systems architecture can be implemented in the HLA by creating federates for each subsystem and defining the data communicated between subsystems in terms of HLA’s data model. HLA’s default communication model defines publishers and subscribers of data classes. The HLA provides class based filtering, i.e., a federate only receives data for a data class to which it has subscribed. However, HLA’s default communication model has no notion of direct ‘wiring’ between federates. Thus, it is not possible to have data sent to a specific federate. This creates a problem if multiple instances of a system of systems are simulated concurrently, which may be desirable so as to observe the interactions between systems. In this case, the data sent within one system is exposed to all other systems in the simulation. This thesis explores this problem of simulating multiple systems of systems using the HLA. The problem is stated formally by introducing the concept of a message path and showing that a federation containing multiple systems of systems contains incorrect message paths which communicate intra-system data between systems. Three methods are presented and shown to solve the problem by either eliminating the incorrect message paths or allowing a receiving federate to determine whether intra-system data was delivered via an incorrect message path. The three solutions are Local Data Filtering (LDF), Data Distribution Management (DDM), and Federation Communities (FC). The LDF solution marks all intra-system data with a system identifier, allowing receivers to distinguish whether they should process it. The DDM method uses a service defined by the HLA that essentially provides an automated version of the LDF solution. The FC method restricts one federation to simulating one system and requires a multiple system simulation to enable inter-federation communication, something that is not defined in the HLA. These three methods are analysed both quantitatively and qualitatively. The quantitative analysis looks at performance overhead imposed by each method and how well each method reduces the number of incorrect intra-system messages communicated. The qualitative analysis is presented in terms of identifying the complexity of implementing each method for a specific systems of systems federation: the election process for the Australian federal government. The thesis concludes that the LDF method is simple to understand but potentially finicky to implement and is wasteful of network resources. The DDMmethod is advantageous in that it is a service defined by the HLA standard. However, the implementation of the DDM services by a Runtime Infrastructure (RTI) is not defined by the HLA. Thus, the performance of the DDMmethod is coupled to a specific RTI and its configurability. The FC method achieves an ideal of replicating the simulation of a single system without modification to achieve a multisystem simulation. However, it requires and inter-federation communicationmechanism that is not defined by the HLA. The FC method introduces extra latency and reduced throughput to inter-system messages in a Local Area Network (LAN) environment. / Thesis (Ph.D.) -- University of Adelaide, School of Computer Science, 2009

Ulm, Univ. Diss., 2006.

Freiburg i. Br., Universiẗat, Diss., 2009.

Thesis (Ph. D.)--University of Missouri--Columbia, 1996. / "May 1996" Typescript. Vita. Includes bibliographical references (l. [167]-204). Also available on the Internet.