Dissertations / Theses on the topic 'GPX'

The aim of this work is to study and theoretically process existing movement options of station in OPNET Modeler environment. These options are described in first part. Furthermore to design and implement function to display path obtained from real-world conditions and done to station following this route during simulation. Coordinates used to move station are obtained by GPX format, which is used to store clearly the GPS coordinates. Second part is devoted to describing creation of this function, first using PHP script, then direct implementation into OPNET Modeler environment using C++.

Cells are continuously facing an oxidative challenge induced by free radicals. These may be generated in different way, i. e. by electron escaping the mitochondrial transport chain, activity of the NADPH oxidase and nitric oxide synthase family of enzymes and autoxidation of favoenzymes. However, the radicals superoxide (*O2- ) and nitric oxide (NO*) do not appear so destructive when produced in tissues. The abundance of superoxide dismutases (SODs) assures that O2*- is immediately dismutated to O2 and the apparently less dangerous H2O2. In pathologic conditions, however, H2O2 is used to produce hypoclorous acid (HOCl) and similarly reactive compounds by the heme peroxidases of leukocytes, or the hydroxyl radical (OH*) by Fenton-like chemistry. Similarly, under these conditions, peroxynitrite (ONOO-) -the reaction product between NO* and *O2- - is transformed into more toxic species. Interestingly, no enzyme has so far been discovered that could detoxify OH*, RO*, singlet oxygen, or HOCl. Evidently, nature was sage enough not to embark in this effort, due to the difficulty to compete with the diffusion-limited reaction of these species on biological targets. However living cells are continuously facing an oxidative challenge and self-protection appears mandatory. This is essentially achieved by preventing radical formation from hydroperoxides (R-OOH) and ONOO-. Interestingly, this appears particularly relevant on the light of the observation that these species may act as mediators of diverse physiological responses such as cell proliferation, differentiation and migration. The enzymes involved in mammals to handle R-OOH and ONOO-, belong to two distinct protein families, the glutathione peroxidases (GPxs) and the peroxiredoxins (Prxs). Both act on H2O2 and on ONOO- -although ONOO- is generally believed to be a better substrate for Prx than GPxs- and, also, on a wide spectrum of alkyl hydroperoxides comprising the products of lipoxygenases. GPxs are widely distributed in nature, from bacteria to humans. They use either selenium or sulfur in the redox center that is oxidized by the hydroperoxide, thus forming an oxidized enzyme intermediate, which is regenerated in its reduced form by a reductant. This is not always glutathione (GSH), as the name of the family should suggest. The redox center is remarkably conserved in the whole family and it is made of a catalytic tetrad containing Sec or Cys, Gln, Trp and Asn. When it contains selenium, as it typically occurs in mammalian GPx -the ‘SecGPxs’- the oxidized intermediate formed upon reaction of the catalytic moiety with the R-OOH -believed to be a selenol (SeO-)- is reduced by GSH. In this reaction a selenodisulfide intermediate is formed, that is displaced by a second GSH, yielding GSSG and reduced enzyme. When it contains sulphur, instead, as in the GPxs of non-vertebrates and plants (CysGPxs), the reducing substrate is a Trx or a ‘redoxin’ of the Trx family, and an intrachain disulphide is the oxidized intermediate of the enzyme. This mechanism requires, besides the ‘peroxidatic Cys ‘(CP), a second ‘resolving Cys’ (CR). The sole monomeric SecGPx of vertebrates -GPx4- does not bear the CR residue, is active on GSH and, obviously, does not form the intermediate intrachain selenodisulfide. The ‘canonic mechanism’ of GPxs, involving a CR when the redox center is a CP instead of a ‘peroxidatic Sec’ (UP) and the consequent use of Trx or ‘redoxins’ as the reducing substrate for the intermediate disulphide (CP - CR) has been challenged by the discovery of GPx7 and GPx8 in mammals. These are two monomeric GPxs of the endoplasmic reticulum (ER), containing a CP but missing a Cys residue –located within the aminoacid stretch of the alpha 4 helix of the GPx thioredoxin fold- where the CR residue of non-vertebrate and plants GPxs is found. Here, GPx7 has been characterized as the prototype of these unusual 1CysGPx. Although at low levels, GPx7 is widely distributed in tissues. Both, its NH2-terminal peptide and the C terminal KREDL motif proved to be functional to ER entrance and retention respectively. Kinetic studies on GPx7 have been carried out using phospholipid hydroperoxides, the most appropriate for monomeric GPxs, using the enzyme expressed in E. coli, fused with synuclein to overcome an otherwise very poor expression. From steady state kinetics the rate constant for the oxidation of the active site resulted rather high (k+1=9.5 x E03 M-1sec-1), whilst the rate of the regeneration of the catalyst by GSH remarkably low (k’+2=12.6 M-1sec-1). Unexpectedly, the oxidized active site is instead rapidly reduced by a ‘redoxin’, protein disulfide isomerase (PDI) (k’+2=3.5 x E03 M-1sec-1), but not by Trx. This evidence was corroborated by the affinity constant for PDI measured by SPR (KD= 5.2 µM). Furthermore the presence in GPx7 of a Cys residue replacing the resolving function of the CR of non-vertebrates and plants GPxs, was ruled out by mutagenesis. Thus, the ‘canonical mechanism’ by which in GPx a CR is required for being reduced by a ‘redoxin’ does not apply to GPx7. This enzyme indeed accepts electrons from a ‘redoxin’ such as PDI by a mechanism involving the CP only. GPx7, and the structurally similar GPx8, therefore, represent rare exceptions within the family of glutathione peroxidases, for being 1CysGPx preferentially reduced by a ‘redoxin’. In fact the GPxs family is mostly contributed by the non-vertebrates ‘2CysGPx’ that are functionally Trx peroxidases. Although these data frame the physiological function of GPx7 in the area of oxidative folding of proteins in ER, no evidence was obtained in this respect. Searching for adaptive response to ER stress alternative to the unfolded protein response (UPR), we observed increased phosphorylation of the extracellular signal regulated kinase 1-2 (ERK 1-2) by GPx7 silencing following a proliferative stimulus by the fibroblast growth factor (FGF). These data finalize the enzymatic characterization of GPx7 as a ‘non-canonical’ member of the GPxs family, do not support the role in ER stress but envisage a role in the cross talk between the redox status of ER and growth factor signaling.
Le cellule vanno continuamente incontro a ‘stress ossidativo’ indotto da radicali liberi. Questi possono essere generati in diversi modi, ad esempio da elettroni che sfuggono alla catena respiratoria mitocondriale, dall'attività delle NADPH ossidasi o dalle ossido nitrico sintasi e dalla autossidazione di flavoenzimi. Tuttavia, i radicali superossido (*O2-) e ossido nitrico (NO*) non appaiono così distruttivi per i tessuti. L'abbondanza di superossido dismutasi (SOD) assicura che l’ *O2- sia immediatamente dismutato a O2 e H2O2, una sostanza apparentemente meno pericolosa. Ciò non toglie che, in condizioni patologiche, l’H2O2 possa essere usata per produrre acido ipocloroso (HOCl) e altri composti reattivi dalle eme perossidasi dei leucociti, oppure per produrre il radicale idrossile (OH*) attraverso la reazione di Fenton. Allo stesso modo, in queste condizioni, il perossinitrito (ONOO-), prodotto di reazione tra NO* e *O2-, si trasforma in specie più tossiche. È interessante notare il fatto che non sia stato mai trovato enzima capace di detossificare OH*, RO*, ossigeno singoletto, oppure HOCl. Evidentemente, la natura è stata saggia abbastanza da non impegnarsi in uno sforzo impossibile, per la difficoltà di competere con l’altissima reattività di queste specie su bersagli biologici, limitata solo dalla diffusione. Tuttavia le cellule devono costantemente affrontare ‘stress ossidativo’ e pertanto l’autoprotezione è obbligatoria. Questa è perseguita prevenendo la formazione di radicali dagli idroperossidi (R-OOH) e dal perossinitrito. Ciò è particolarmente rilevante alla luce del fatto che queste sostanze stanno emergendo come mediatori di diverse risposte fisiologiche quali la proliferazione, la differenziazione e la migrazione cellulare. Gli enzimi dei mammiferi implicati nella detossificazione degli R-OOH e ONOO- appartengono a due distinte famiglie di proteine, le glutatione perossidasi (GPxs) e le peroxiredossine (Prx). Entrambi agiscono sull’H2O2 o sul ONOO- - anche se, generalmente il ONOO- è ritenuto substrato migliore per le Prx rispetto alle GPxs – e, inoltre, su un ampio spettro di idroperossidi alchilici comprendenti i prodotti della lipossigenasi. Le GPxs sono ampiamente distribuite in natura, dai batteri all'uomo. Utilizzano sia selenio che zolfo nel centro catalitico ossidoriduttivo, che viene ossidato dall’R-OOH, formando così un intermedio ossidato che viene rigenerato da un agente riducente. Questo non è sempre glutatione (GSH), come il nome di questa famiglia di enzimi potrebbe suggerire. Il centro redox delle GPxs è notevolmente conservato in tutta la famiglia ed è costituito da una tetrade catalitica composta da Sec o Cys, Gln, Trp e Asn. Quando contiene selenio, come tipicamente nelle GPx dei mammiferi – le ‘SecGPxs’-, l’intermedio ossidato, formatosi dalla reazione del centro catalitico con l’R-OOH, probabilmente il selenolo (SeO-), viene ridotto dal GSH, il quale forma un intermedio selenodisulfuro che viene poi ridotto da una seconda molecola di GSH, con produzione di GSSG ed enzima ridotto. Quando invece contiene zolfo, come tipicamente nelle GPxs dei non-vertebrati e nelle piante (CysGPxs), il substrato riducente è una preferenzialmente la tioredossina (Trx) o una ‘redossina’ della famiglia delle Trxs, e l'intermedio ossidato dell’enzima è un disolfuro intracatena. Per questo è necessario, oltre alla ‘Cys perossidasica’ (CP), un secondo residuo di Cys la ‘Cys resolving’ (CR). L'attuale, unica SecGPx monomerica nei vertebrati - la GPx4- non presenta il residuo CR, è ridotta dal GSH e ovviamente non forma un intermedio selenodisulfuro intracatena. Il ‘meccanismo canonico’ delle GPxs, che implica quindi una CR quando il centro redox è una CP invece di una Sec perossidasica (UP) e quindi l’uso di preferenziale di Trx o altre ‘redossine’ come substrato riducente, è stato rimesso in discussione dalla scoperta, nei mammiferi, di due nuove GPx, la GPx7 e la GPx8. Queste sono due GPx monomeriche del reticolo endoplasmatico (ER), contenenti una CP, senza un residuo di Cys nello ‘stretch’ di aminoacidi dove si trova la CR delle altre CysGPx dei non-vertebrati e delle piante. In questa tesi, abbiamo caratterizzato la GPx7, come prototipo di queste insolite ‘1CysGPx’. Anche se a bassi livelli, la GPx7 è ampiamente distribuita nei tessuti. Il peptide segnale presente all’estremità NH2-terminale e il motivo C-terminale KREDL sono funzionali per l’ingresso e la ritenzione nell’ER, rispettivamente. Gli studi cinetici sulla GPx7 sono stati effettuati su idroperossidi fosfolipidi (PL-OOH), il substrato più appropriato per le GPxs monomeriche, utilizzando enzima espresso in E. coli, fuso con sinucleina per ottenere alti livelli di espressione. Dalla cinetica in stato stazionario, la costante cinetica per l'ossidazione del sito attivo è risultata piuttosto elevata (k+1=9.5 x E03 M-1sec-1), mentre costante cinetica per la rigenerazione del catalizzatore con GSH notevolmente bassa (k’+2=12.6 M-1sec-1). Sorprendentemente, il sito attivo ossidato è invece rapidamente ridotto da una ‘redossina’, la protein disulfide isomerase (PDI) (k’+2=3.5 x E03 M-1sec-1) ma non dalla Trx. L’interazione PDI-GPx7 è stata confermata dalla misura della costante di affinità della GPx7 per la PDI mediante SPR (KD= 5.2 µM). Inoltre è stata esclusa, mediante mutagenesi, la eventuale presenza nella GPx7 di un residuo Cys che possa fare la funzione della CR tipica delle GPxs dei non-vertebrati e delle piante. Quindi, il ‘meccanismo canonico’ mediante il quale nelle GPxs è richiesta una CR per essere ridotte da una ‘redossina’ non si applica alla GPx7 (e probabilmente neanche alla GPx8, che è strutturalmente simile). Questo enzima infatti, accetta elettroni da un ‘redossina’ come la PDI attraverso un meccanismo che implica la sola CP. La GPx7 (e la GPx8) si configurano quindi come insolite ‘1CysGPx’ della famiglia delle glutation perossidasi, poiche’ sono di fatto rare eccezioni. Infatti, la famiglia delle glutation perossidasi è per la maggior parte composta da ‘2CysGPx’ dei non-vertebrati e delle piante che sono funzionalmente Trx perossidasi. Sebbene questi dati sembrerebbero inquadrare la funzione fisiologica della GPx7 nel ‘protein folding’ che avviene nell’ER, nessuna evidenza è stata da noi ottenuta in questo senso. In cerca di una risposta adattativa alternativa all’unfolded protein response (UPR), abbiamo osservato un aumento di fosforilazione della extracellular signal regulated kinase 1-2 (ERK 1-2) in seguito al silenziamento della GPx7 dopo uno stimolo proliferativo con il fattore di crescita dei fibroblasti (FGF). Questi dati finalizzano la caratterizzazione enzimatica della GPx7 come un membro ‘non-canonico’ della famiglia delle GPxs, non suggeiscono un ruolo nello stress del ER, ma indicano invece un ruolo nel cross talk tra lo stato redox del ER e segnali provenienti da fattori di crescita.

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The antioxidant action of organic selenium compounds, as well as ebselen and diphenyl diselenide (DPDS), is closely connected to its ability of generating the selenol group. (In) this study it was evaluated the in vitro antioxidant effect of new mono and diselenide compounds, where it was compared whether the formation of p-methyl-selenol from compounds 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1,2-dip-tolyldiselenide (C4) and o-methoxy-selenol from compounds 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and 1,2-bis(2-methoxyphenyl) diselenide (C3) may be involved with their antioxidant effects. The mono and diselenide compounds were tested in their Fe(II) and sodium nitroprusside (SNP)-induced lipid peroxidation in rat brain and liver homogenates and also in their antioxidant ability in phosphomolybdenum test-reductionand and DPPH radical. Besides, the effects of the compounds in the antioxidant enzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) were quantified. The new compounds oxidant effects were investigated through the thiol oxidase assay and the cellular viability of isolated leukocytes. The results demonstrated that the compounds obtained a significant reduce on the lipid peroxidation induced by different pro-oxidants, as well as an antioxidant effect similarly when compared to ascorbic acid equivalents. In the same manner, the compounds did not present thiol oxidase activity. Furthermore, they did not preset any decrease on the cellular viability of leucocytes. The compounds C1 and C2 did not show mimetic activity of GPx enzyme or had a substrate effect on TrxR enzyme, probably due the amino group presence on their chemical structures which must have inhibited the selenol formation. However, DPDS analog-compounds presented a mimetic activity of GPx, as well as they showed an increase in the TrxR activity, presumably due the formation of the selenol groups (p-methyl-selenol and o-methoxy-selenol).
A ação antioxidante dos compostos orgânicos de selênio, como o ebselen e o disseleneto de difenila (DPDS), está intimamente envolvida com a capacidade de formação do grupamento selenol. Neste estudo foi avaliado o perfil antioxidante in vitro de novos compostos mono e disseleneto, onde foi comparado se a formação do p-metil-selenol pelos compostos 1-fenil-3-(p-tolilselenil)propano-2-amina (C1) e o 1,2-dip-tolildisseleneto (C4), assim como a formação do grupamento o-metoxi-selenol pelos compostos 1-(2-metoxifenilselenil)-3-fenilpropano-2-amina (C2) e 1,2-bis(2-metoxifenil)disseleneto (C3) pode estar associados com os efeitos antioxidantes apresentados. Os novos compostos mono e disseleneto foram avaliados quanto a capacidade de redução dos níveis de peroxidação lipídica induzida por Fe(II) e nitroprussiato de sódio em homogenatos de cérebro e fígado de ratos, assim como também foi avaliada a capacidade antioxidante através do ensaio da redução do fosfomolibdênio e do radical DPPH. Além disso, foram quantificados os efeitos dos compostos quanto à atividade das enzimas antioxidantes, tioredoxina redutase (TrxR) e glutationa peroxidase (GPx). O efeito oxidante, dos novos compostos, foi investigado através do ensaio da tiol oxidase e da viabilidade celular de leucócitos isolados. Decorrente dos resultados obtidos foi possível evidenciar que ambos os compostos apresentaram uma redução significativa da peroxidação lipídica quando induzidas por diferentes pro oxidantes assim como, uma capacidade antioxidante total semelhante a equivalentes de acido ascórbico. Da mesma forma, os compostos não apresentaram efeito tiol oxidase, assim como não apresentaram uma diminuição da viabilidade celular de leucócitos. Os compostos C1 e C2 não apresentaram atividade mimética a enzima GPx assim como, também não serviram de substrato para a enzima TrxR, provavelmente devido a presença do grupamento amino nas estruturas químicas destas moléculas o que incapacitou a formação dos respectivos grupamentos selenois. No entanto, os compostos análogos ao DPDS apresentaram atividades miméticas a GPx, assim como também apresentaram uma aumento na atividade da TrxR provavelmente devido a formação dos selenois (p-metil-selenol e o-metoxi-selenol).

This master thesis describes development of Photography Geotagging Application from an introduction to the issues, through the analysis and design to the resulting implementation. The reader should be able understand to issues of time in geotagging using the GPS tracks records. He will also understand where and how metadata are stored. The big part of thesis is dedicated to the implementation of application which leads the reader through building the application architecture, the photography representation and loading their metadata with program ExifTool. Gradually will be explained the convertors of coordinates and GPS track parsers, which are used to synchronization. The final application allows the user synchronize photography with GPS track and display them on the map.

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O papel fisiolÃgico das peroxidases de glutationa (GPX) da mitocÃndria em plantas à muito pouco conhecido. Suas relaÃÃes com a fotossÃntese sÃo desconhecidas, ainda mais na presenÃa de estresse salino. Essa enzima possui grande importÃncia na remoÃÃo de H2O2 e hidroperÃxidos orgÃnicos, contribuindo na proteÃÃo oxidativa e na homeostase redox. Neste estudo, mutantes de arroz silenciados nos genes OsGPX1 ou OsGPX3, das proteÃnas mitocondriais, foram utilizados para entender os mecanismos fisiolÃgicos do papel dessa enzima no crescimento e fotossÃntese. Adicionalmente, estes processos foram estudados tambÃm em condiÃÃes de estresse salino para as plantas silenciadas em OsGPX1. Os resultados mostram, pela primeira vez, que a deficiÃncia de uma GPX mitocondrial à capaz de restringir o crescimento vegetal por deficiÃncia na fotossÃntese. Este efeito deve ser causado indiretamente por mudanÃas nas redes genÃticas e metabÃlicas desencadeadas por alteraÃÃes nos nÃveis de H2O2 (aumentado) e/ou glutationa reduzida (diminuÃda). à provÃvel que o estado redox alterado em mitocÃndrias pelo efeito da GPX possa aumentar a fotossÃntese atravÃs da comunicaÃÃo entre esta organela e cloroplastos por mecanismos ainda nÃo estabelecidos. AlÃm disso, o gene OsGPX1 mostrou ter papel significativo no controle do movimento estomÃtico, que à crucial para a eficiÃncia do uso da Ãgua sob condiÃÃo de estresse salino. As GPX mitocondriais tambÃm parecem estar envolvidas com a dissipaÃÃo do excesso de energia luminosa na forma de calor (NPQ) no aparato do fotossistema II e na rota da fotorrespiraÃÃo. Em conclusÃo, o gene OsGPX1, associado com seu produto proteico e mudanÃas desencadeadas nas redes metabÃlicas e gÃnicas, sÃo essenciais para o crescimento de arroz pelo aumento da fotossÃntese, especialmente a nÃvel de eficiÃncia de uso da luz envolvendo atividade do fotossistema II e eficiÃncia quÃntica do CO2 em condiÃÃes normais de crescimento. Adicionalmente, a GPX1 aparenta mostrar uma importÃncia menor para a resistÃncia ao estresse salino.
The physiological role of glutathione peroxidases (GPX) in plant mitochondria is little known. Their relations with the photosynthesis are unknown, even more in presence of salt stress. This enzyme have great importance in H2O2 and organic hydroperoxides scavenging, contributing in oxidative protection and redox homeostasis. In this study, silenced rice mutants in OsGPX1 and OsGPX3 genes, coding for the mitochondrial proteins, were used to better understand the physiological mechanisms of the role of this protein in growth and photosynthesis. Additionally, these processes were also studied in salt stress conditions with the plants silenced in OsGPX1. The results show, for the first time, that the lacking of a mitochondrial GPX is capable of restricting plant growth by impairment in photosynthesis. This response might be an indirect consequence of changes in gene and metabolic networks trigged by alterations in H2O2 (raised) and/or reduced glutathione (diminished). It is likely that the altered redox state in mitochondria by GPX effects can improve photosynthesis through cross-talk between this organelle and chloroplasts by yet unknown mechanisms. Furthermore, the OsGPX1 gene showed significant role in stomatal control, which is crucial to the water use efficiency under salt stress conditions. The mitochondrial GPX also seems to be involved with dissipation of excess light energy as heat (NPQ) in photosystem II apparatus and in photorespiratory pathway. In conclusion, the OsGPX1 gene, associated with it protein product and changes in gene and metabolic networks, are essential to rice growth by improvement of photosynthesis, especially at light use efficiency level involving photosystem II activity and CO2 quantum efficiency in normal and growth conditions. Additionally, GPX1 seems to be less important to salt stress tolerance.

Os recém-nascidos possuem o sistema antioxidante imaturo, por haver baixa tensão de oxigênio no ambiente intrauterino durante a vida fetal. Logo após o nascimento, as alterações súbitas das condições fisiológicas e ambientais causam significativo aumento no consumo de oxigênio, desencadeando, assim, a produção de radicais livres. Tais condições promovem vulnerabilidade dos neonatos ao efeito negativo do estresse oxidativo, o que potencialmente podem prejudicar a vitalidade neonatal. O presente estudo teve como objetivo comparar o perfil antioxidante e estresse oxidativo de neonatos e fêmeas caninas no periparto eutócico vaginal ou cesariana eletiva, e avaliar a influência da condição obstétrica para o estado oxidativo. Foram selecionadas 21 cadelas gestantes, as quais, constituíram dois grupos amostrais, de acordo com a condição obstétrica: Eutocia Vaginal (n = 10) e Cesariana Eletiva (n = 11); e seus respectivos neonatos foram alocados em subgrupos de acordo com a condição obstétrica e momento do nascimento: Eutocia Vaginal Inicial (n=10), Eutocia Vaginal Final (n = 9), Cesariana Eletiva Inicial (n = 11) e Cesariana Eletiva final (n= 10). As cadelas foram avaliadas no período pródromo do parto, intraparto; uma hora e três dias pós-parto, quando amostras de sangue foram colhidas para análise do perfil antioxidante [dosagem das enzimas superóxido dismutase (SOD), glutationa peroxidase (GPx), dosagem da concentração de tióis totais e determinação do status antioxidante total(TAC)] e do estresse oxidativo [dosagem da peroxidação lipídica (TBARS) e da oxidação de proteínas]. Os neonatos foram avaliados quanto ao escore Apgar aos 0 e 60 minutos do nascimento; avaliação clínica (frequências cardíaca e respiratória; escore de tônus muscular, irritabilidade reflexa e coloração de mucosa, aferição da temperatura corporal), lactatemia sanguínea, oximetria de pulso, determinação do perfil antioxidante e do estresse oxidativo e aferição do peso corporal aos 0, 60 minutos, às 12, 24 horas e ao 3º dia pós nascimento. As cadelas do Grupo Eutocia Vaginal apresentaram maior peroxidação lipídica, oxidação de proteínas e atividade de SOD e menor atividade de GPx e concentração de tióis totais em comparação ao Grupo Cesariana Eletiva. A capacidade antioxidante total elevou-se após 1h do parto em comparação aos outros momentos de avaliação no Grupo Cesariana Eletiva. Embora os neonatos do Grupo Eutocia Vaginal tenham apresentado melhores parâmetros de vitalidade neonatal, em comparação ao Grupo Cesariana Eletiva, todos os neonatos apresentaram adequada evolução do escore Apgar, coloração de mucosa, irritabilidade reflexa, tônus muscular e oxigenação periférica após 1h do nascimento. A lactatemia sanguínea foi maior no Grupo Eutocia Vaginal, bem como nos neonatos nascidos ao final do parto. A peroxidação lipídica foi superior nos neonatos nascidos por eutocia vaginal em comparação aos nascidos por cesariana eletiva, enquanto a oxidação de proteínas mostrou-se maior nos primeiros neonatos nascidos por eutocia vaginal em comparação aos nascidos ao final do parto. Porém, resultado contrário foi verificado para o Grupo Cesariana Eletiva, pois os neonatos nascidos ao final da cirurgia apresentaram maior valor de oxidação de proteínas. Ademais, para os neonatos nascidos ao final do parto, o Grupo Cesariana Eletiva apresentou maior oxidação proteica em comparação ao Grupo Eutocia Vaginal. A atividade da GPx foi superior nos neonatos nascidos por cesariana eletiva. Em conclusão, a condição obstétrica impõe diferenças no perfil oxidativo e antioxidante em cadelas e neonatos, os quais apresentam estado oxidativo semelhante, denotando influência materna sobre o equilíbrio oxidativo dos recém-nascidos.
Newborns have an immature antioxidant system, due to low oxygen exposure in intrauterine environment during fetal life. Immediately after birth, sudden changes of physiological and environmental conditions cause a significant increase in oxygen consumption, resulting in the production of free radicals. These conditions turn the newborn vulnerable to the negative effects of oxidative stress, which potentially can impair neonatal vitality. This study aimed to compare the antioxidant profile and oxidative stress of neonates and canine females during vaginal labour or elective cesarean section, and to evaluate whether the obstetric condition influences their oxidative status. For this purpose, 21 pregnant bitches were subjected to two experimental groups, according to the obstetric condition: Vaginal Eutocia (n = 10) and Elective Cesarian Section (n = 11) and their respective newborns were allocated into subgroups according to the obstetric condition and moment of birth: Inicial Vaginal Eutocia (n=10), Final Vaginal Eutocia (n = 9), Inicial Elective Cesarian Section (n = 11) and Final Elective Cesarian Section (n= 10). Bitches were evaluated during the preparatory phase of whelping, intrapartum; one and 72 hours postpartum, when blood samples were collected for analysis of the antioxidant profile [Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) activity enzymes assays, Total Antioxidant Capacity (TAC) assay and Total Thiols Concentration assay] and oxidative stress [lipid peroxidation (TBARS) and protein oxidation assays]. Neonates were evaluated for the Apgar score at 0 and 60 minutes of birth; clinical evaluation (heart and respiratory rates; muscle tone, irritability reflex and mucous color score; and body temperature), blood lactate, pulse oximetry, determination of antioxidant profile and oxidative stress, and body weight measurement at 0, 60 minutes, 12, 24 and 72 hours after birth. The Vaginal Eutocia bitches had higher lipid peroxidation, protein oxidation and SOD activity and lower GPx activity and total thiols concentration in comparison to the Elective Cesarian Section Group. Total antioxidant capacity was higher 1 hour postpartum compared to the others evaluation moments in the Elective Cesarian Section Group. Although neonates from the Vaginal Eutocia Group presented better neonatal vitality than those from the Elective Cesarian Section, all neonates presented adequate evolution of the Apgar score, mucous color, irritability reflex, muscle tone and pulse oximetry 1 hour postpartum. Blood lactatemia was higher in the Vaginal Eutocia Group, as well as for the last neonates. Lipid peroxidation was higher in neonates born by vaginal eutocia compared to those born by elective cesarean section, whereas protein oxidation was higher in the first neonates born by vaginal eutocia compared to those born at the end of delivery. Conversely, Elective Cesarian Section neonates born at the end of surgery had higher protein oxidation. In addition, for those neonates born at the end of delivery, the Elective Cesarian Section group presented higher protein oxidation compared to the Vaginal Eutocia group. Furthermore, GPx activity was higher in neonates born by elective caesarean section. In conclusion, the obstetric condition imposes differences in the oxidative and antioxidant profile in bitches and neonates with similar oxidative status, denoting maternal influence on the oxidative balance of the newborns.

La contaminazione da micotossine può coinvolgere tutti i comparti della filiera agroalimentare e rappresenta a tutti gli effetti un potenziale di perdita economica. Il settore zootecnico è particolarmente esposto alle ricadute della contaminazione, in termini di costi sanitari per gli effetti cronici sulla salute animale conseguenti all’esposizione alle micotossine. La prevenzione in campo mediata da appropriate tecniche agronomiche rappresenta, per quanto ovvio, la più importante strategia per ridurre la contaminazione dei mangimi. Un approccio completamente differente è quello che si basa sulla possibilità di ridurre gli effetti delle tossine sull’animale, modificando la sua alimentazione attraverso l’integrazione nutrizionale di opportuni agenti chemiopreventivi. Numerose sono le specie chimiche, di origine naturale o sintetica, che hanno dimostrato una efficacia chemiopreventiva del danno ossidativo indotto da micotossine ed emergono per la loro efficacia il selenio e i suoi composti organici ed inorganici. L’azione antineoplastica del selenio è nota da molto tempo e ha trovato conferme in numerosi studi epidemiologici che indicano una relazione inversa tra assunzione di selenio con la dieta e rischio di sviluppo di una patologia neoplastica. Questa tesi di dottorato ha avuto come obiettivo la progettazione, la sintesi e lo studio di composti diamminoacidici contenenti un atomo di calcogeno (selenio o zolfo), mimici dalla glutatione perossidasi (GPx) e auspicabilmente attivi nel contrasto del danno ossidativo indotto dall’aflatossina B1 (AFB1). Le specie diamminoacidiche sintetizzate appartengono alla classe dei Sec-derivati, ovvero sono costitute da un residuo di L-selenocisteina (o L-cisteina) a cui è legato attraverso l’atomo di calcogeno un altro L-amminoacido. Alla porzione calcogenica, che rappresenta il sito redox, sono stati infatti ancorati rispettivamente un residuo di L-prolina modificata e un residuo di L-leucina. Al termine delle fasi di sintesi e caratterizzazione chimico-fisica dei calco-diamminoacidi è stata intrapresa una serie di indagini biochimiche in collaborazione con due distinti laboratori in Germania. I risultati ottenuti hanno permesso di dimostrare che alcuni Sec-derivati sono in grado di ridurre i perossidi attraverso un meccanismo catalitico che mima l’attività della GPx. Essi sembrano inoltre evidenziare che il “meccanismo antiossidante” sia mediato sostanzialmente dall’attività GPx mentre non sono particolarmente attivi meccanismi di radical scavenging né di puro trasferimento elettronico. Alcuni dei Sec-derivati sintetizzati sono stati oggetto di un’indagine cellulare preliminare volta a verificare una eventuale effettiva azione protettiva dei calco-diamminoacidi verso il danno cellulare indotto da AFB1. Le indagini sono state effettuate adoperando una linea cellulare HepG2. I dati ottenuti, nel loro insieme, hanno mostrato che i calco-diamminoacidi esaminati sono di per sé caratterizzati da una notevole attività biologica. In particolare, alla concentrazione più elevata utilizzata (100 µM), alcuni di essi hanno mostrato interessanti proprietà citoprotettive contro il danno indotto da AFB1. L’efficacia è paragonabile, e in qualche caso superiore, a quella riscontrabile per il composto di riferimento, la Se-metil-selenocisteina, principale forma di selenio organico che è naturalmente presente in specie vegetali quali Allium Sativum e Brassica juncea.
Mycotoxin contamination may involve all fields of the food agricultural chain and might potentially determine economic losses. In particular, the livestock sector is at risk of health costs, as a consequence of chronic diseases induced by mycotoxin exposure. It is obvious, although actual, that the mycotoxin contamination should be controlled on the field by a series of suitable agriculture practices in order to minimize the mycotoxin formation in feeds. Recently, dietary strategies (antioxidant compounds, medicinal herbs, plant extracts) to counteract the effects of mycotoxins have attracted considerable attention. Chemoprevention refers to the use of naturally occuring and/or synthetic chemicals to inhibit the development of mycotoxin induced chronic diseases. Selenium and its organic and inorganic compounds, have emerged as outstanding chemoprevention agents. Selenium antineoplastic properties have been well documented through the last decades, being supported by several epidemiological evidences on the association between selenium intake and the risk for some kinds of human/animal cancers. This PhD thesis was focussed on design, synthesis and study of a family of chalcogenic diamino acids (containing either selenium or sulfur), GPx mimics and potentially active to reduce the oxidative damage induced by aflatoxin B1 (AFB1). The diamino acids synthesized belong to the family of Sec-derivatives and consist of L-selenocysteine (or L-cysteine) linked through the calchogen atom to either a L-proline or a L-leucine moiety. The GPx-like catalytic activity of the various compounds was confirmed using both thiophenol and GPx assays. Their possible radical-scavenging activity, and electron-donor reducing character as well, could be ruled out by suitable assays. The cytoprotective capacity exhibited by several of the compounds synthesized was investigated in HepG2 cells by MTS assays. The results indicated that all the chalcogenic diamino acids tested had a strong biological activity. In particular, the pre-treatment of the test cells with two Sec-derivatives, employed at higher doses (100 µM), led to a protective effect on cell toxicity, lowering the AFB1-induced cell mortality, and this efficacy is comparable with that of the reference Se-metil-selenocysteine, main source of organic selenium in plants such as Allium Sativum and Brassica juncea.

La contaminazione da micotossine può coinvolgere tutti i comparti della filiera agroalimentare e rappresenta a tutti gli effetti un potenziale di perdita economica. Il settore zootecnico è particolarmente esposto alle ricadute della contaminazione, in termini di costi sanitari per gli effetti cronici sulla salute animale conseguenti all’esposizione alle micotossine. La prevenzione in campo mediata da appropriate tecniche agronomiche rappresenta, per quanto ovvio, la più importante strategia per ridurre la contaminazione dei mangimi. Un approccio completamente differente è quello che si basa sulla possibilità di ridurre gli effetti delle tossine sull’animale, modificando la sua alimentazione attraverso l’integrazione nutrizionale di opportuni agenti chemiopreventivi. Numerose sono le specie chimiche, di origine naturale o sintetica, che hanno dimostrato una efficacia chemiopreventiva del danno ossidativo indotto da micotossine ed emergono per la loro efficacia il selenio e i suoi composti organici ed inorganici. L’azione antineoplastica del selenio è nota da molto tempo e ha trovato conferme in numerosi studi epidemiologici che indicano una relazione inversa tra assunzione di selenio con la dieta e rischio di sviluppo di una patologia neoplastica. Questa tesi di dottorato ha avuto come obiettivo la progettazione, la sintesi e lo studio di composti diamminoacidici contenenti un atomo di calcogeno (selenio o zolfo), mimici dalla glutatione perossidasi (GPx) e auspicabilmente attivi nel contrasto del danno ossidativo indotto dall’aflatossina B1 (AFB1). Le specie diamminoacidiche sintetizzate appartengono alla classe dei Sec-derivati, ovvero sono costitute da un residuo di L-selenocisteina (o L-cisteina) a cui è legato attraverso l’atomo di calcogeno un altro L-amminoacido. Alla porzione calcogenica, che rappresenta il sito redox, sono stati infatti ancorati rispettivamente un residuo di L-prolina modificata e un residuo di L-leucina. Al termine delle fasi di sintesi e caratterizzazione chimico-fisica dei calco-diamminoacidi è stata intrapresa una serie di indagini biochimiche in collaborazione con due distinti laboratori in Germania. I risultati ottenuti hanno permesso di dimostrare che alcuni Sec-derivati sono in grado di ridurre i perossidi attraverso un meccanismo catalitico che mima l’attività della GPx. Essi sembrano inoltre evidenziare che il “meccanismo antiossidante” sia mediato sostanzialmente dall’attività GPx mentre non sono particolarmente attivi meccanismi di radical scavenging né di puro trasferimento elettronico. Alcuni dei Sec-derivati sintetizzati sono stati oggetto di un’indagine cellulare preliminare volta a verificare una eventuale effettiva azione protettiva dei calco-diamminoacidi verso il danno cellulare indotto da AFB1. Le indagini sono state effettuate adoperando una linea cellulare HepG2. I dati ottenuti, nel loro insieme, hanno mostrato che i calco-diamminoacidi esaminati sono di per sé caratterizzati da una notevole attività biologica. In particolare, alla concentrazione più elevata utilizzata (100 µM), alcuni di essi hanno mostrato interessanti proprietà citoprotettive contro il danno indotto da AFB1. L’efficacia è paragonabile, e in qualche caso superiore, a quella riscontrabile per il composto di riferimento, la Se-metil-selenocisteina, principale forma di selenio organico che è naturalmente presente in specie vegetali quali Allium Sativum e Brassica juncea.
Mycotoxin contamination may involve all fields of the food agricultural chain and might potentially determine economic losses. In particular, the livestock sector is at risk of health costs, as a consequence of chronic diseases induced by mycotoxin exposure. It is obvious, although actual, that the mycotoxin contamination should be controlled on the field by a series of suitable agriculture practices in order to minimize the mycotoxin formation in feeds. Recently, dietary strategies (antioxidant compounds, medicinal herbs, plant extracts) to counteract the effects of mycotoxins have attracted considerable attention. Chemoprevention refers to the use of naturally occuring and/or synthetic chemicals to inhibit the development of mycotoxin induced chronic diseases. Selenium and its organic and inorganic compounds, have emerged as outstanding chemoprevention agents. Selenium antineoplastic properties have been well documented through the last decades, being supported by several epidemiological evidences on the association between selenium intake and the risk for some kinds of human/animal cancers. This PhD thesis was focussed on design, synthesis and study of a family of chalcogenic diamino acids (containing either selenium or sulfur), GPx mimics and potentially active to reduce the oxidative damage induced by aflatoxin B1 (AFB1). The diamino acids synthesized belong to the family of Sec-derivatives and consist of L-selenocysteine (or L-cysteine) linked through the calchogen atom to either a L-proline or a L-leucine moiety. The GPx-like catalytic activity of the various compounds was confirmed using both thiophenol and GPx assays. Their possible radical-scavenging activity, and electron-donor reducing character as well, could be ruled out by suitable assays. The cytoprotective capacity exhibited by several of the compounds synthesized was investigated in HepG2 cells by MTS assays. The results indicated that all the chalcogenic diamino acids tested had a strong biological activity. In particular, the pre-treatment of the test cells with two Sec-derivatives, employed at higher doses (100 µM), led to a protective effect on cell toxicity, lowering the AFB1-induced cell mortality, and this efficacy is comparable with that of the reference Se-metil-selenocysteine, main source of organic selenium in plants such as Allium Sativum and Brassica juncea.

Le système antioxydant joue un rôle clef dans la réponse de la plante au stress. Parmi ce système antioxydant, les expressions de gènes codant des protéines similaires aux glutathions peroxydases (GPX) sont activées chez Helianthus annuus infecté par Plasmopara halstedii, agent du mildiou du tournesol, et chez Lycopersicon esculentum suite à une stimulation mécanique. Le travail présenté dans ce mémoire consiste à mieux comprendre le rôle de ces protéines notamment dans la réponse au stress. Pour cela plusieurs approches complémentaires ont été envisagées : 1) la caractérisation de l'expression de différents gènes de GPX dans des conditions de stress biotiques et abiotiques ; 2) la caractérisation des activités enzymatiques in vitro de ces protéines ; 3) l'étude de leur distribution tissulaire et leur localisation cellulaire ; 4) l'analyse de la réponse aux stress de plantes transgéniques dont l'expression de gènes codant pour des isoformes de GPX est modifiée

Lo scopo di questa tesi è stata la reingegnerizzazione del modulo di Geographic Information System (GIS) di Alchemist, ovvero quella parte che si occupa di caricare ed utilizzare i dati di tipo geografico, come mappe terrestri e tracce GPS. L’obbiettivo primario di questo lavoro è stato creare una struttura in grado di garantire la possibilità di caricare le tracce GPS in vari formati. A tal scopo si è prodotto un caricatore di tracce che, applicando il pattern Strategy, delega il caricamento dei vari formati di tracce e l’allineamento dei tempi ad entità esterne al fine di massimizzare l’estendibilità. Infine per validare il modello e l’implementazione si sono prodotti dei test automatici.

Einleitung: Es ist wenig darüber bekannt, wie sich das antioxidative System von Kälbern nach der Geburt entwickelt, welche Faktoren darauf Einfluss nehmen und wie sich antioxidative Parameter in ihren Aktivitäten resp. Konzentrationen unter physiologischen Bedingungen verändern. Zielstellung: Ziel dieser Arbeit war es zum einen die altersabhängige Entwicklung antioxidativer Parameter bei gesunden Kälbern und Jungrindern bis zum 18. Lebensmonat zu verfolgen und zum anderen zu evaluieren, ob bei metabolisch gering belasteten Jungrindern jahreszeitliche Differenzen bezüglich Superoxiddismutase (SOD), Glutathionperoxidase (GPX) und Trolox Equivalent Antioxidative Capacity (TEAC) bestehen. Material und Methoden: Es wurden gesunde weibliche Kälber bzw. Jungrinder der Rasse Holstein Friesian / Deutsche Schwarzbunte aus drei Betrieben am 1. (n = 33) und 7. (n = 31) Tag sowie im 1. (n = 33), 3. (n = 33), 6. (n = 5), 9. (n = 5), 12. (n = 32) und 18. (n = 31) Monat post natum (p. n.) klinisch und labordiagnostisch untersucht. Weiterhin wurden in einem Betrieb während eines Jahres im September, November, Januar, März, Mai und Juli jeweils 6 gesunde weibliche Jungrinder, die zum Untersuchungszeitpunkt 12 Monate alt waren, kontrolliert. Die Tiere wurden im Stall in Anbindehaltung gehalten, ausgenommen der im Mai in Weidehaltung untersuchten Tiere. Analysiert wurden im Blut die antioxidativen Parameter SOD, GPX und TEAC, der Hämatokrit (Hkt) und die Stoffwechselparameter Gesamtprotein, Albumin, Bilirubin, Haptoglobin, Harnstoff, Cholesterol, ß-Hydroxybutyrat (BHB), AST, AP, GLDH, CK, Ca, anorganisches Phosphat (Pi) und Fe. Ergebnisse: Ein betrieblicher Einfluss war statistisch nicht nachweisbar. Vom 1. Tag bis zum 18. Monat p. n. zeigten die antioxidativen Parameter SOD, GPX und TEAC einen gleichartigen Verlauf mit einem kontinuierlichen Anstieg bis zum 6. Monat p. n.. Die GPX-Aktivitäten stiegen von 50-80 U/ml Hkt am 1. Tag p. n. auf 100-190 U/ml Hkt im 6. Monat p. n. an. Die niedrigsten Aktivitäten (p<0,05) bestanden am 1. und 7. Tag (62-90 U/ml Hkt) p. n.. Die SOD-Aktivitäten am 1. (4500-5600 U/g Hb) und 7. Tag (4600-5450 U/g Hb) p. n. waren niedriger als im 1. (5400-6800 U/g Hb) und 3. Monat (5600-7800 U/g Hb) p. n. (p<0,05). Der Anstieg der TEAC-Konzentration vom 1. Tag p. n. (220-290 µmol/l) zum 6. Monat p. n. (260-340 µmol/l) war nicht signifikant. Nach dem 6. Monat p. n. fielen die Akti-vitäten resp. Konzentrationen ab, wobei die SOD-Aktivitäten mit 12 (4000-5000 (U/g Hb) und 18 Monaten (3700-5000 U/g Hb) p. n. signifikant niedriger waren als im 1. und 3. Mo-nat p. n.. Die GPX-Aktivitäten lagen mit 12 (118-152 U/ml Hkt) und 18 Monaten (105-150 U/ml Hkt) p. n. signifikant über denen der ersten Lebenswoche. Die TEAC-Konzentrationen waren im 12. Monat p. n. mit 260-320 µmol/l größer als vom 1. Tag bis zum 1. Monat (240-280 µmol/l) p. n. (p<0,05). Die SOD, GPX und TEAC korrelierten außer mit 9 Monaten p. n. zu allen Untersuchungszeitpunkten signifikant positiv. Für AST, AP, CK und Bilirubin wurden am 1. Tag p. n. die signifikant höchsten Aktivitäten resp. Konzen-trationen ermittelt, für Haptoglobin am 7. Tag p. n.. Gesicherte Korrelationen bestanden zwischen Albumin, Bilirubin und der TEAC, zwischen BHB und TEAC, GPX sowie SOD außerdem zwischen Ca und Pi. Im Jahresverlauf waren die GPX-Aktivitäten im September und Januar mit 73-103 U/ml Hkt niedriger als von März bis Juli mit 104-142 U/ml Hkt (p<0,05). Erniedrigte TEAC-Konzentrationen wurden besonders im Januar (272-302 µmol/l) und signifikant im März (265-299 µmol/l) gegenüber September und November (319-345 µmol/l) ermittelt. Die SOD-Aktivitäten differierten nicht gesichert. GPX und SOD korrelierten im ganzen Jahr gesichert, TEAC und SOD außer im Januar ebenfalls, GPX und TEAC nur im November, März, Mai und Juli. Die Stoffwechselparameter befanden sich im physiologischen Bereich, mit Ausnahme von Harnstoff im November und Juli sowie Pi im Mai. Schlussfolgerungen: Es wird geschlussfolgert, dass das antioxidative System der neu-geborenen Kälber zur Geburt noch unreif ist und sich bis zum sechsten Monat p. n. stabilisiert. Die durch den Abbau des fetalen Hämoglobins und die Vormagenentwicklung vermehrt entstehenden ROS tragen zu einer weiteren Aktivitäts- resp. Konzentrationssteigerung der antioxidativen Parameter bis zu einem Maximum im 6. Monat p. n. bei. Danach stellt sich ein Gleichgewicht zwischen Pro- und Antioxidantien ein. Auf die GPX-Aktivitäten und TEAC-Konzentrationen konnte ein jahreszeitlicher Einfluss bei Jungrinden ermittelt werden.

Nahrungsinhaltsstoffe sind im Organismus an Steuerungsprozessen und Stoffwechselvorgängen beteiligt, wobei die Mechanismen ihrer Wirkung noch nicht völlig aufgeklärt sind. Wie Vitamin E zeigen auch sekundäre Pflanzeninhaltsstoffe in Zellsystemen sowie in vivo eine Reihe biologischer Wirkungen, deren Erklärung jedoch häufig auf ihre antioxidative Eigenschaft reduziert wird. Ziel der Dissertation war es, den Einfluss von Vitamin E und anderen Pflanzeninhaltsstoffen (in Form von Pflanzenextrakten oder isolierten sekundären Pflanzeninhaltsstoffen, z.B. Polyphenole), die bisher alle hauptsächlich als Antioxidanz klassifiziert wurden, auf die transkriptionelle Regulation von Phase I- und Phase II-Enzymen zu untersuchen. Dazu wurde die Aktivierung des PXR (pregnane X receptor) und des Nrf2 (NF-E2-related factor-2) als zentrale Transkriptionsfaktoren der Phase I- bzw. Phase II-Enzyme getestet.

Der Einfluss von verschiedenen Vitamin E-Formen und antioxidativen Pflanzeninhaltsstoffen in Form von Reinsubstanzen (Curcumin, EGCG, Medox, Quercetin, Resveratrol und Sulforaphan) oder Pflanzenextrakten (aus Blaubeeren, Gewürznelken, Himbeeren, Nelkenpfeffer, Thymian oder Walnüssen) auf die Aktivierung von PXR und Nrf2 sowie des Promotors eines jeweiligen Zielgens (CYP3A4 bzw. GI-GPx) wurde in vitro mit Reportergenplasmiden untersucht. Es zeigte sich, dass sowohl Vitamin E-Formen als auch verschiedene sekundäre Pflanzeninhaltsstoffe PXR und/oder Nrf2 sowie die Promotoren der jeweiligen Zielgene CYP3A4 bzw. GI-GPx aktivieren. In einem Tierexperiment konnte diese genregulatorische Wirkung von Vitamin E auf die in vivo-Situation übertragen werden. In Lebern von Mäusen, deren Futter unterschiedliche Mengen von Vitamin E enthielt (Mangel-, Normal- und Überflussdiät), wurde eine direkte Korrelation zwischen der alpha-Tocopherol-Konzentration und der Cyp3a11 mRNA-Expression nachgewiesen (Cyp3a11 ist das murine Homolog zum humanen CYP3A4). Entgegen der in vitro-Situation hatte gamma-Tocotrienol in vivo einen nur kaum nachweisbaren Effekt auf die Expression der Cyp3a11 mRNA, induzierte aber die Expression der alpha-TTP mRNA. Es konnte gezeigt werden, dass Vitamin E und sekundäre Pflanzeninhaltsstoffe Phase I- und Phase II-Enzyme transkriptionell regulieren können.

Die Wirkungen des Vitamin E können sich allerdings nur entfalten, wenn die Vitamin E-Formen ausreichend vom Körper aufgenommen werden. Gegenstand der Dissertation waren daher auch Untersuchungen zur Bioverfügbarkeit (zelluläre Akkumulation und Metabolismus) verschiedener Vitamin E-Formen. Es konnte gezeigt werden, dass Unterschiede in der chemischen Struktur der Vitamin E-Formen deren zelluläre Akkumulation und Metabolisierung beeinflussen.

Unter Berücksichtigung der Ergebnisse der Dissertation lassen sich protektive Wirkungen von antioxidativen Nahrungsinhaltsstoffen auch unabhängig von ihren antioxidativen Eigenschaften über die Induktion zelleigener Schutzsysteme, einschließlich der Phase I- und Phase II-Enzyme, erklären. Die Induktion der zelleigenen Abwehr lässt sich auch als adaptive Antwort (sog. "adaptive response") des Organismus gegenüber zellschädigenden Ereignissen betrachten.
In the organism food compounds are involved in regulatory and metabolic processes although the mechanisms of their effects have not been completely elucidated yet. Like vitamin E, secondary plant compounds have diverse biological effects, both in cell systems as well as in vivo. However, the explanation thereof is often reduced to their antioxidative capacity. The aim of this thesis was to investigate the influence of vitamin E and other plant compounds (in form of plant extracts or isolated secondary plant compounds, e.g. polyphenols), which were up to now classified primarily as antioxidants, on the transcription of phase I- and phase II-enzymes. For this, the activation of central transcription factors of the phase I- or phase II enzymes, PXR (pregnane X receptor) and Nrf2 (NF-E2-related factor-2), was tested.

The influence of different vitamin E forms and antioxidative plant compounds in form of pure substances (curcumin, EGCG, Medox, quercetin, resveratrol, and sulforaphane) or plant extracts (from blueberries, clove, raspberries, allspice, thyme, or walnuts) on the activation of PXR and Nrf2 as well as on the promoter of a respective target gene (CYP3A4 or GI-GPx) was investigated in vitro by reporter gene assays. It appeared that vitamin E forms as well as different secondary plant compounds activate PXR and/or Nrf2 as well as the promoter of the respective target genes CYP3A4 and GI-GPx. The effects of vitamin E were confirmed in vivo by an animal experiment. In livers of mice whose diet contained different amounts of vitamin E (deficient, adequate and supra-nutritional), a direct correlation between alpha-tocopherol content and Cyp3a11 mRNA expression was shown (Cyp3a11 is the murine homolog to the human CYP3A4). In contrast to the in vitro observations, gamma-tocotrienol in vivo only had a small effect on the expression of Cyp3a11 mRNA. However, it induced the expression of alpha-TTP on mRNA level. It could be shown that vitamin E and secondary plant compounds can influence the transcriptional regulation of phase I- and/or phase II-enzymes.

However, these effects of vitamin E can only be seen if the vitamin E forms are taken up by the body sufficiently. Therefore, another aim of the thesis was to investigate the bioavailability of different vitamin E forms (i.e., cellular accumulation and metabolism). It could be shown that differences in the chemical structure of vitamin E forms influence their cellular accumulation and metabolism.

Regarding the results of this thesis, protective effects of antioxidative food compounds can be explained independent of their antioxidative properties by the induction of cellular protective systems, including phase I- and phase II-enzymes. The induction of cellular defence mechanism can also be considered as an adaptive response of the organism towards cell-damaging events.

This thesis deals with design, development and testing of device for collecting fly data in ultralight airplane or helicopter. The basic collected value is a count of fly hours of each pilot. Additional fly data are latitude, longitude and altitude. Purpose of this device is a fair pricing for use of the airplane. Another utilization is in analysis of flight path or in pilot training. This device is succesfully made from miniature computer Raspberry Pi and uses GPS data. A reader will be informed about aviation regulations, embedded systems, global positioning system and wireless internet connection.

Gene expression of the biotransformation enzymes, glutathione S-transferase (GST) glutathione peroxidase (GPx) and glutathione synthesizing enzyme glutamyl-cysteine-ligase (GCL), was investigated in zebrafish (Dani orerio) exposed to arsenate, perchlorate, a mixture of these two chemicals, and thyroxine (T4). The exposure persisted for 30 days for perchlorate, 7 days for arsenate and 7 days for thryroxin. To test the mixture toxicity of arsenate and perchlorate, arsenate was added for 7 days in addition to 30 days exposure to perchlorate. Arsenate is known to induce oxidative stress, and GCL, GPx, and GST are involved in the oxidative stress response. Thyroid hormone is involved in mediating the oxidative stress response, and perchlorate is a known thyroid gland disruptor. Therefore, this research was designed to test the hypotheses that 1) thyroid hormone affects the gene expression of GCL, GPx, and GST enzymes and 2) thyroid hormone modulates As-induced expression of these genes. Fish were exposed to the mixture of arsenate and perchlorate to examine the effect of thyroid hormone on As-induced gene expression of GCL, GPx, and GST. The findings indicate that arsenate up-regulates the transcription of GCL and GST pi genes in the gills and GSTpi gene in liver, and this induction was not observed in presence of perchlorate. Therefore, it can be concluded that thyroid hormone inhibits As-induced gene expression of GCL and GSTpi.

Das 1817 erstmals schriftlich erwähnte Selen galt lange Zeit nur als toxisch und sogar als procancerogen, bis es 1957 von Schwarz und Foltz als essentielles Spurenelement erkannt wurde, dessen biologische Funktionen in Säugern durch Selenoproteine vermittelt werden. Die Familie der Glutathionperoxidasen nimmt hierbei eine wichtige Stellung ein. Für diese sind konkrete Funktionen und die dazugehörigen molekularen Mechanismen, welche über die von ihnen katalysierte Hydroperoxidreduktion und damit verbundene antioxidative Kapazität hinausgehen, bislang nur unzureichend beschrieben worden.

Die Funktion der gastrointestinalen Glutathionperoxidase (GI-GPx) wird als Barriere gegen eine Hydroperoxidabsorption im Gastrointestinaltrakt definiert. Neuen Erkenntnissen zufolge wird die GI-GPx aber auch in verschiedenen Tumoren verstärkt exprimiert, was weitere, bis dato unbekannte, Funktionen dieses Enzymes wahrscheinlich macht.
Um mögliche neue Funktionen der GI-GPx, vor allem während der Cancerogenese, abzuleiten, wurde hier die transkriptionale Regulation der GI-GPx detaillierter untersucht. Die Sequenzanalyse des humanen GI-GPx-Promotors ergab das Vorhandensein von zwei möglichen "antioxidant response elements" (ARE), bei welchen es sich um Erkennungssequenzen des Transkriptionsfaktors Nrf2 handelt. Die meisten der bekannten Nrf2-Zielgene gehören in die Gruppe der Phase-II-Enzyme und verfügen über antioxidative und/oder detoxifizierende Eigenschaften. Sowohl auf Promotorebene als auch auf mRNA- und Proteinebene konnte die Expression der GI-GPx durch typische, in der Nahrung enthaltene, Nrf2-Aktivatoren wie z.B. Sulforaphan oder Curcumin induziert werden. Eine direkte Beteiligung von Nrf2 wurde durch Cotransfektion von Nrf2 selbst bzw. von Keap1, das Nrf2 im Cytoplasma festhält, demonstriert. Somit konnte die GI-GPx eindeutig als Nrf2-Zielgen identifiziert werden. Ob sich die GI-GPx in die Gruppe der antiinflammatorischen und anticancerogenen Phase-II-Enzyme einordnen lässt, bleibt noch zu untersuchen.

Die Phospholipidhydroperoxid Glutathionperoxidase (PHGPx) nimmt aufgrund ihres breiten Substratspektrums, ihrer hohen Lipophilie und ihrer Fähigkeit, Thiole zu modifizieren, eine Sonderstellung innerhalb der Familie der Glutathionperoxidasen ein. Mit Hilfe eines PHGPx-überexprimierenden Zellmodells wurden deshalb Beeinflussungen des zellulären Redoxstatus und daraus resultierende Veränderungen in der Aktivität redoxsensitiver Transkriptionsfaktorsysteme und in der Expression atheroskleroserelevanter Adhäsionsmoleküle untersucht. Als Transkriptionsfaktoren wurden NF-kB und Nrf2 ausgewählt. Die Bindung von NF-kB an sein entsprechendes responsives Element in der DNA erfordert das Vorhandensein freier Thiole, wohingegen Nrf2 durch Thiolmodifikation von Keap1 freigesetzt wird und in den Kern transloziert. Eine erhöhte Aktivität der PHGPx resultierte in einer Erhöhung des Verhältnisses von GSH zu GSSG, andererseits aber in einer verminderten Markierbarkeit freier Proteinthiole. PHGPx-Überexpression reduzierte die IL-1-induzierte NF-kB-Aktivität, die sich in einer verminderten NF-kB-DNA-Bindefähigkeit und Transaktivierungsaktivität ausdrückte. Auch war die Proliferationsrate der Zellen vermindert. Die Expression des NF-kB-regulierten vaskulären Zelladhäsionsmoleküls, VCAM-1, war ebenfalls deutlich verringert. Umgekehrt war in PHGPx-überexprimierenden Zellen eine erhöhte Nrf2-Aktivität und Expression der Nrf2-abhängigen Hämoxygenase-1 zu verzeichnen. Letzte kann für die meisten der beobachteten Effekte verantwortlich gemacht werden.

Die hier dargestellten Ergebnisse verdeutlichen, dass eine Modifizierung von Proteinthiolen als wichtige Determinante für die Regulation der Expression und Funktion von Glutathionperoxidasen angesehen werden kann. Entgegen früheren Vermutungen, welche oxidative Vorgänge generell mit pathologischen Veränderungen assoziierten, scheint ein moderater oxidativer Stress, bedingt durch eine transiente Thiolmodifikation, durchaus günstige Auswirkungen zu haben, da, wie hier dargelegt, verschiedene, miteinander interagierende, cytoprotektive Mechanismen ausgelöst werden. Hieran wird deutlich, dass sich "antioxidative Wirkung" oder "oxidativer Stress" keineswegs nur auf "gute" oder "schlechte" Vorgänge beschränken lassen, sondern im Zusammenhang mit den beeinflussten (patho)physiologischen Prozessen und dem Ausmaß der "Störung" des physiologischen Redoxgleichgewichtes betrachtet werden müssen.
Selenium was discovered in 1817 by the Swedish chemist Berzelius and was for a long time considered as being toxic and even procarcinogenic. In 1957, however, Schwarz and Foltz realized that selenium is an essential trace element which elicits its biological functions in mammals as a structural component of selenoproteins among which the family of glutathione peroxidases plays a dominant role. Glutathione peroxidases reduce hydroperoxides to the corresponding alcohols and contribute to the antioxidative capacity of a cell. However, other functions of glutathione peroxidases and the according molecular mechanisms have hardly been described.>br>
The gastrointestinal glutathione peroxidase (GI-GPx) is believed to build a barrier against the absorption of foodborne hydroperoxides. In addition, GI-GPx expression is increased in different tumors. This indicates further, still unknown, functions of this enzyme.
In order to elucidate new possible functions of GI-GPx, especially during carcinogenesis, the transcriptional regulation of GI-GPx was analyzed in more detail. An analysis of the GI-GPx promoter sequence revealed the presence of two putative "antioxidant response elements" (ARE) which are recognition sites for the transcription factor Nrf2. Most of the known Nrf2 target genes either belong to the group of phase-II detoxification enzymes or possess antioxidative and/or detoxifying properties. On promoter level as well as on mRNA- and protein level the expression of GI-GPx was induced by typical Nrf2-activating compounds such as sulforaphane or curcumin that are contained in the diet. A direct involvement of Nrf2 was demonstrated by cotransfection of Nrf2 itself or by cotransfection of Keap1 which retains Nrf2 in the cytosol. Thus, the GI-GPx gene was unequivocally identified as a new target for Nrf2. Whether GI-GPx also belongs in the category of antiinflammatory and anticarcinogenic enzymes remains to be elucidated.

The phospholipid hydroperoxide glutathione peroxidase (PHGPx) is exceptional among the glutathione peroxidases because of its broad range of substrates, its high lipophilicity, and its ability to modify protein thiols. With PHGPx-overexpressing cells, the influence of PHGPx on the cellular redox state and on resulting changes in the activity of redox-sensitive transcription factors and on the expression of proatherogenic adhesion molecules was analyzed. For this, the redox-sensitive transcription factors NF-kB and Nrf2 were chosen. NF-kB requires free thiols for being able to bind to its responsive element within the DNA, whereas Nrf2 is released from Keap1 and translocates to the nucleus upon a modification of protein thiols. PHGPx-overexpression resulted in an increase in the ratio of GSH to GSSG, in a reduced amount of intracellular protein thiols, and in a diminished proliferation rate. Furthermore, PHGPx-overexpressing cells displayed a reduced IL-1-dependent NF-kB activity as was assessed by a reduced NF-kB DNA-binding ability and activity of a NF-kB-driven reporter gene. In addition, the expression of the NF-kB-dependent vascular cell adhesion molecule (VCAM-1) was also inhibited by overexpression of PHGPx. On the other hand, PHGPx-overexpressing cells displayed an increased activity of Nrf2 that was accompanied by an increased expression of the Nrf2-dependent heme oxygenase-1. Heme oxygenase-1 most likely is responsible for most of the aforementioned effects.

The data presented here show that a modification of protein thiols can be regarded as an important determinant for the regulation and for the functions of glutathione peroxidases. In contrast to the previous assumption that oxidative processes are always linked to pathologic changes, a moderate oxidative stress seems to have beneficial effects, because it triggers different cytoprotective mechanisms. It can be concluded that the terms "antioxidative effect" or "oxidative stress" cannot simply be restricted to "good" or "bad" processes, but need to be seen in context with the modulated (patho)physiological processes and the degree of "disturbance" of the physiologic redox balance.

L'altération de la fonction mitochondriale, β-cellules pancréatiques, et l'homéostasie du glucose de la descendance de rat de l'exerciceContexte. Il est connu que l'environnement gestationnel est reconnue comme un facteur essentiel pour le développement du fœtus et étroitement liée à l'état de santé dans la vie plus tard. Environnement inadéquat pour le fœtus tels que le stress oxydatif intra-utérine est très nocif pour le développement du fœtus. Par conséquent, un effort de prévention de surmonter ce problème est nécessaire en modifiant l'environnement autour de la gestation par l'exercice durant cette période.Objectifs. Le but de cette étude était de connaître le rôle des mitochondries dans la prévention du stress oxydatif pendant la grossesse, en augmentant système antioxydant et la fonction du pancréas et dans l'amélioration de l'homéostasie du glucose de l'enfant de la mère qui a été induite par l'exercice régulier d'intensité modérée.Méthodes. Cette étude a été réalisée au Laboratoire de bioénergétique appliquée et fondamentale Inserm U1055, Université Joseph Fourier, Grenoble-France. Les sujets étaient rat Wistar femelle qui ont été divisés en 2 groupes, le groupe sédentaire et l'exercice. L'entraînement physique a été effectué 4 semaines avant et jusqu'à ce que le 18e jour de la gestation. Thiol et GPx ont été mesurées en utilisant un dosage biochimique. Consommation d'O2 a été mesurée avec oxygraphie. L'activité du complexe respiratoire, cytochrome et ROS ont été mesurées par spectrophotométrie. Citrate synthase, la protéine kinase B (PKB), quinone et tocophérol ont été mesurées en utilisant un dosage biochimique. La graisse viscérale et du pancréas total ont été pesés, et la taille de l'île de Langerhans a été analysé par la préparation de l'histologie. Les résultats ont été analysés en utilisant le test t.Résultats. Il a été constaté que l'état redox du nouveau-né est égal. La diminution de thiol suivie par une augmentation de l'activité antioxydante GPx (p <0,001). L'efficacité de la consommation et de l'activité du complexe respiratoire, suivie par une augmentation de cytochrome, la quinone et du tocopherol oxygène provoque la diminution de la production de ROS de la progéniture de rat de levées mère (p <0,001). La sécrétion d'insuline a augmenté de 74% et l'activité PKB était plus élevée (p <0,05). Tolérance au glucose et de l'insuline (âgés de 3 mois) étaient mieux (p <0,05), la taille de l'île de Langerhans et le poids du pancréas étaient plus petits (p = 0,021) chez la progéniture de rat de l'exercice mère. À l'âge de 3 mois, le taux de glucose dans le sang était inférieur de 8% (p = 0,046), l'insuline à jeun était plus élevé de 72% (p = 0,009) et le poids corporel était inférieur (p = 0,041) de la progéniture de rat de l'exercice mère par rapport à ceux de la mère sédentaire, mais le total de graisse viscérale était pas différente (p> 0,05).Conclusion. L'exercice régulier d'intensité modérée pour la mère de 4 semaines avant et jusqu'à ce que le 18e jour de la gestation a été très efficace pour augmenter le système antioxydant et réduire le stress oxydatif dans la grossesse qui est en mesure de réduire le risque d'obésité pour la progéniture par l'amélioration de l'homéostasie du glucose à travers l'augmentation des mitochondries et la fonction pancréatique de la progéniture de rat. L'altération des mitochondries et la fonction du pancréas que l'impact de l'exercice régulier de la mère est permanente pendant l'observation puisque le bébé est né, âgé de 21 jours et 3 mois.Mots-clés: exercice, programmation fœtale, l'homéostasie du glucose, insuline, les mitochondries, l'obésité, le stress oxydatif, β-cellules pancréatiques, les espèces réactives de l'oxygène
Influence de l'environnement (exercice et nutrition) durant la gestation sur l’état de stress oxydant et le métabolisme du glucose de la descendance.Les maladies métaboliques sont en pleine expansion dans nos sociétés actuelles et constituent un enjeu de santé publique majeur. Les antécédents familiaux, l'environnement et les habitudes de vie de l'individu vont jouer un rôle dans la susceptibilité à certains de ces désordres métaboliques. Sur la base de données épidémiologiques, un lien a été établi entre environnement durant les premières phases de la vie et survenue de pathologies à l'âge adulte conduisant au concept des "Developmental Origins of Health and Diseases" (DOHaD). Le premier objectif de ce travail était d'étudier, à partir d'un modèle murin, les conséquences de l'exercice physique quotidien de la mère pendant la gestation sur la composition corporelle, le statut oxydant, la fonction pancréatique et mitochondriale du foie et du muscle et la gestion des substrats énergétiques de la descendance. Un deuxième objectif était de valider un modèle de diabète gestationnel à partir d’un régime riche en fructose et d’étudier l’effet d’une supplémentation en fer durant ce diabète gestationnel sur le statut oxydant et la tolérance au glucose des mères et de la descendance. Nos résultats montrent une réduction significative de la production mitochondriale d’H2O2, un indicateur de la production d’espèces réactives de l’oxygène, dans le foie et dans le muscle des petits de mères entrainées. Ces changements sont reliés à des altérations de la consommation d’oxygène mitochondriale, de la composition des membranes mitochondriales et de l’activité des enzymes antioxydantes. De plus, l'entraînement maternel avant et pendant la gestation est associé à des modifications de la structure et de la fonction du pancréas de la descendance et semble modifier sa gestion des substrats énergétiques.Nous avons également confirmé qu’une diète riche en fructose durant la gestation peut être utilisée comme un modèle induisant un diabète gestationnel. Nous avons ainsi démontré chez les petits nés de mères nourries avec un régime riche en fructose et en fer, que les activités des enzymes antioxydantes comme la glutathion peroxidase (GPx), la glutathion-S-transferase dans le foie et la GPx dans le cerveau étaient altérées, les résultats étant différents selon le sexe des petits. Les différents résultats obtenus chez la descendance montrent que dans le cas d’un diabète gestationnel, les fœtus sont plus sensibles que leurs mères aux effets d’un régime riche en fer. Ce travail de thèse vient compléter les travaux menés dans le cadre des DOHaD et renforce l'idée que l'environnement lors des premières phases de la vie va avoir des conséquences sur la santé de l'individu.Mots-clés : exercice, gestation, descendance, mitochondries, stress oxydant, diabète gestationnel, fer, régime riche en fructose

O chumbo (Pb) é um metal altamente tóxico no qual os sinais de intoxicação variam bastante ao considerar as diferenças interindividuais. Um dos principais mecanismos de toxicidade do Pb ocorre pela inibição da enzima ácido delta aminolevulínico desidratase (ALAD) no sistema hematopoiético. O Pb também desempenha um importante papel no desbalanço do estado redox, pois sabe-se que ele tem o potencial de aumentar a concentração de espécies reativas de oxigênio (EROS) e inibir enzimas antioxidantes, como por exemplo a glutationa peroxidase (GPx). No entanto, poucos estudos avaliaram estes parâmetros em população ocupacionalmente exposta brasileira. Assim, o presente estudo, objetiva estudar a correlação entre as concentrações de Pb no sangue (Pb-S) de trabalhadores de fábricas de bateria e as atividades das enzimas ALAD e GPx associados com os polimorfismos genéticos da ALAD e GPx. Para tal, foram utilizadas 278 amostras de sangue de trabalhadores expostos ao Pb. As determinações de Pb foram realizadas por espectrometria de massas com plasma acoplado indutivamente (ELAN DRCII Perkin- Elmer). As genotipagens dos polimorfismos genéticos da ALAD e da GPx foram realizadas pela Reação em Cadeia da Polimerase (PCR) em tempo real e as atividades das enzimas ALAD e GPx foram determinadas no sangue por espectrofotometria de UV/VIS. A média da concentração de Pb-S foi de 22,8 ± 14,7 ?g/dL. Foram observadas correlações negativas entre Pb-S e atividade da ALAD (rs -0,24 p<0,01) e Pb-S e atividade de GPx (rs -0,27 p<0,05). Também foi verificada correlação negativa entre a porcentagem de inibição da ALAD e a atividade de GPx (rs -0,21 p<0,01). Em relação aos polimorfismos genéticos, não observamos associação entre os genótipos do ALAD (? -0,19 P>0,05) e GPx (genótipo CT: ? -1,37 P>0,05; genótipo TT: ? -8,37 P>0,05) e a concentração de Pb-S. Não foram observadas associações entre o polimorfismo rs1800668 e a atividade de GPx (genótipo CT: ? -0,016 P>0,05; genótipo TT: ? -0,004 P>0,05). No entanto, foi constatada uma associação entre o genótipo ALAD 1-1 do polimorfismo rs1800435 e a atividade da enzima ALAD (? 3,5 P<0,05). Neste sentido, os resultados deste estudo mostram que o genótipo ALAD 1-1 do polimorfismo rs1800435 do gene ALAD está associado a uma maior atividade da enzima ALAD nos indivíduos expostos ao Pb. Além disso, o polimorfismo rs1800668, localizado no gene que codifica a enzima GPx, não modula a atividade desta enzima nos indivíduos expostos ao metal. Ambos os polimorfismos dos genes ALAD e GPx parecem não influenciar nas concentrações de Pb-S na população estudada.
Lead (Pb) is a highly toxic metal which signs of intoxication vary greatly when considering the interindividual differences. One of the main mechanism of toxicity of Pb is due to inhibition of the enzyme acid delta aminolevulinic dehydratase (ALAD) in the hematopoietic system. Pb also plays an important role in the redox state of unbalance, since it is known that it has the potential of increasing the concentrations of reactive oxygen species (ROS) and inhibit antioxidant enzymes such as glutathione peroxidase (GPx). However, few studies have evaluated these parameters in Brazilian population occupationally exposed. Thus, the present study aims to study the correlation between the concentrations of Pb in the blood (B-Pb) of workers of battery factories and the activities of ALAD and GPx enzymes associated with genetic polymorphisms in ALAD and GPx. Then, blood samples of 278 workers exposed to Pb were collected. Pb was measured by Inductively Coupled Plasma-Mass Spectrometry (Perkin-Elmer ELAN DRCII). The genotyping of genetic polymorphisms of ALAD and GPx was performed by Real-Time Polymerase Chain Reaction (PCR) and activity of ALAD and GPx enzymes in the blood was determined by spectrophotometry UV / VIS. The mean concentration of B-Pb was 22.81 ± 14.73 mg / dL. Negative correlation was found between B-Pb and ALAD activity (rs -0.24 p < 0.01) and B-Pb and GPx activity (rs -0.27 p < 0.05). There was also a negative correlation between the percentage of inhibition of ALAD and GPx activity (rs -0.21 p < 0.01). Considering the genetic polymorphisms, no association between ALAD genotypes (? -0.19 P < 0.05) and GPx (CT genotype: ? -1.37 P > 0.05, TT genotype : ? -8.37 P > 0.05 ) and the concentration of B-Pb. No association between rs1800668 polymorphism and GPx activity (CT genotype: ? -0.016 P > 0.05, TT genotype : ? -0.004 P > 0.05). However an association was found between ALAD 1-1 rs1800435 genotype and ALAD enzyme activity (? 3.5 P < 0.05). Accordingly, the results of this study show that the ALAD 1-1 genotype of rs1800435 polymorphism in ALAD gene is associated with increased activity of ALAD enzyme in individuals exposed to Pb. Furthermore the rs1800668 polymorphism located in a gene encoding the enzyme GPx does not modulate the activity of this enzyme in individuals exposed to the metal. Both polymorphisms of ALAD and GPx genes seem to have no influence in the concentrations of B-Pb in the population studied.

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Fundação de Amparo a Pesquisa do Estado de Minas Gerais
Selenium (Se) is one of the essential nutrient for several physiological functions that include activity of the proteins catalytic centre, increase of the immune system functions and reduces the cancer risk, besides being the essential component of the antioxidative enzyme, glutatione peroxydase (GPx). In areas where the soil present low Se concentration, such as the Brazilian soils, the agricultural products also presents low concentrations of this element and this deficiency causes serious risks for the human health. Besides the plants, mushrooms have the capacity to accumulate great quantities of Se, and, this characteristic associated to the elevated nutritional value, being a source of proteins, carbohydrates vitamin B1, B2 and B3, calcium and iron, makes of mushrooms aliments that alleviate various nutritional deficiencies. The bioavailability is defined as the proportion of ingested nutrient that is used for normal physiological functions or stored, so, it must be considered in the nutritional food evaluation. The objective of this work was to enrich and determine the bioavailability of Se in Pleurotus ostreatus mushroom. The mushrooms were produced in coffee rusk as substrate base enriched with different concentration of Se 3,2; 6,4; 12,8; 25,4; 51; 76,4; 102 mg kg-1), using sodium setenite. Biological efficiency (BE) and Se, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, N, P, Pb and Zn concentration were evaluated, in three consecutive flushing, in the same substrate. For Se bioavailability, 64 rats (Wistar) were fed using P. ostreatus mushrooms enriched or not with Se, and as positive control sodium selenite was used. BE of the mushrooms was affected by both flushing number and Se concentration in the substrate. The highest value of BE among 13,06 to 37,56% were observed at the first flushing, white BE among 2,47 to 11,09% were obtained at third flushing which period varied from 43 to 79 days after inoculation. Mushrooms groduced in the substrate with 3.2 mg kg -1 present about 55 μg g-1 of Se in the dry matter. The maximum Se concentration absorbed by the fungus was when it was growth in the substrate with 0.64 mmol kg-1 of Se, although the best use of added Se occurred with 12,8 mg kg-1 where 34% of added Se was present in the mushroom. Biological assay showed that Se present in the mushroom was able to cross the intestinal barrier reaching the blood circulation of the animals. The rats using mushroom Se enriched mushroom presents 700 μg L- 1 of Se in the blood plasma, while ones receiving the same quantity of Se as sodium selenite present about 500 μg L-1 (P<0,05). The plasma GPx enzyme activity was about 2000 nmol min-1 mL-1 in rats fed with all diets (P>0,05). The blood plasma protein showed no difference among diet in relation to chromatographic profiles. The peptide in high concentration was detected at 24 min presenting molecular weight estimated to 7,7 kDa. However, Se concentration in this peptide was 2.76, 6. 90 and 5.27 μg L-1 in animals fed, respectively, without Se, Se enriched mushroom and sodium selenite. Based on these results, it can be concluded that: mushroom production was stimulated by low concentration of Se added to the substrate; BE in the first flushing is higher than second and third; concentration of 12,8 mg kg-1 of Se in the substrate resulted in the best use of added Se; Se in the mushroom was better absorbed bay the animals than when as sodium selenate. Selenium present in the mushroom shows high bioavailability, since Se was detected not only in the blood plasma but also into the seric peptides; Over all, P. ostreatus shows an excellent food source of Se.
O selênio (Se) é um nutriente essencial envolvido em diversas funções fisiológicas que incluem atividade no centro catalítico de proteínas, aumento de funções do sistema imune e redução do risco de câncer, além de ser o componente essencial da enzima antioxidativa glutationa peroxidase (GPx). Em áreas onde os solos têm baixa disponibilidade de Se, como os solos brasileiros, os produtos agrícolas também apresentam baixas concentrações desse elemento e essa deficiência causa graves riscos para a saúde humana. Além das plantas, os cogumelos têm a capacidade de acumular grandes quantidades de Se, e, essa característica associada ao elevado valor nutricional, por ser fonte de proteínas carboidratos vitaminas B1, B2 e B3, cálcio e ferro, faz dos cogumelos alimentos para suprir carências nutricionais diversas. A biodisponibilidade, definida como a proporção de nutrientes ingeridos que é utilizada para funções fisiológicas normais ou armazenados, deve ser considerada na avaliação nutricional de um alimento. O objetivo deste trabalho foi enriquecer e determinar a biodisponibilidade de Se nos cogumelos Pleurotus ostreatus. Os cogumelos foram produzidos em substrato à base de casca de café enriquecido com diferentes concentrações de Se (0; 3,2; 6,4; 12,8; 25.4; 51; 76,4; 102 mg kg-1), na forma de selenito de sódio. Determinou-se a eficiência biológica (EB), as concentrações de Se e também de Ca. Cd, Cu, Fe, K, Mg, Mn, Na, N, P, Pb, Zn, em três colheitas consecutivas do cogumelo em um mesmo substrato Para avaliar a biodisponibilidade do Se 64 ratos da linhagem Wistar, receberam dietas contendo cogumelos P. ostreatus enriquecidos ou não com Se. A EB de P. ostreatus foi afetada tanto pelo número de colheitas quanto pelas doses de Se adicionadas ao substrato. Os maiores valores de EB, situados entre 13,06 e 37,56 foram constatados na primeira colheita. Valores de EB entre 2,47 e 11,09 foram obtidos na terceira colheita, após um período que variou de 43 a 79 dias. Na concentração de 3,2 mg kg-1 de Se os cogumelos apresentaram cerca de 55 ug g-1 de Se na massa seca. A quantidade de Se máxima absorvida pelo fungo ocorreu quando foi adicionada ao substrato 51 mg kg-1 de Se, embora, o melhor aproveitamento do Se tenha ocorrido na concentração de 0,16 mmol kg-1 com absorção de 34 % do Se adicionado. O ensaio biológico mostrou que o Se presente nos cogumelos foi capaz de atravessar a barreira intestinal e atingir a circulação dos animais. Os ratos alimentados com dietas contendo cogumelos enriquecidos com Se apresentaram cerca de 700 ug L-1 de Se no plasma sangüíneo, enquanto os alimentados com a mesma quantidade de Se na forma de selenito de sódio apresentaram cerca de 500 ug L-1 (P<0,05). A atividade da enzima Gpx plasmática foi de cerca de 2000 nmol mm-1 mL-1 nos animais que se alimentaram de dietas contendo ou não cogumelos enriquecidos com Se (P>0,05). A análise protéica do plasma sangüíneo por cromatografia mostrou não haver diferença no perfil cromatográfico das amostras. O peptídeo em maior concentração foi detectado aos 24 min de corrida cromatográfica e foi estimado o peso molecular de, aproximadamente, 7,7 kDa. Entretanto, a concentração de Se nesse peptídeo foi 2,76, 6,90 e 5,27 ug L-1, respectivamente nos ratos alimentados sem Se, com cogumelos enriquecidos com Se e com selenito de sódio. Com base nestes resultados pode-se concluir que o selenito de sódio adicionado ao substrato em concentrações de 3,2 a 12,8 mg kg-1 estimulou a produção de cogumelos que foram capazes de acumular Se quando cultivados na presença desse elemento, a EB foi maior na primeira colheita do cogumelo; as concentrações de 3,2 e 12,8 mg kg-1 resultaram em 34% de aproveitamento do Se adicionado ao substrato; o Se presente no cogumelo foi mais absorvido pelos animais do que o Se na forma de selenato de sódio; o Se presente no cogumelo está não só no plasma sangüíneo como também è metabolizado e inserido nos peptídeos séricos; o cogumelo P. ostreatus pode ser uma excelente fonte alimentar de Se.

Selenoproteine spielen eine wichtige Rolle in der antioxidativen Abwehr und bei Immunreaktionen. Der Selen(Se)metabolismus wird von Hepatozyten gesteuert, die das Se-Transportprotein Selenoprotein P (SEPP) synthetisieren und sezernieren. SEPP nimmt bei kritischen Erkrankungen, z. B. Sepsis ab und führt zu niedrigen Se-Spiegeln. Sepsis triggert die übermäßige Produktion von proinflammatorischen Zytokinen. Aminoglykosid-Antibiotika (AG), die oft bei schwerer Sepsis eingesetzt werden, induzieren Fehlinterpretationen der mRNA inklusive des Stoppcodons UGA welches für die Selenoprotein-Biosynthese notwendig ist. Es wurden daher die molekularen Wechselwirkungen zwischen den Zytokinen IL-6, IL-1b und TNFa, AG und dem Se-Status mit der Biosynthese in Leberzelllinien untersucht. IL-6 führte zu einer starken Reduktion der SEPP-mRNA und einer dosisabhängigen Reduktion von SEPP. Parallel dazu reduzierte IL-6 das Transkriptlevel, die Proteinexpression und die Enzymaktivität der Typ-I-Dejodase (DIO1). Auf die Expression der antioxidativ-wirkenden Glutathionperoxidasen (GPX) wirkte IL-6 isozymspezifisch; während die Transkriptkonzentrationen von GPX2 anstiegen und die von GPX4 abnahmen, blieb GPX1 unbeeinflusst. Die IL-6-abhängigen Effekte bestätigten sich auch in Reportergenassays von SEPP-, DIO1-, GPX2- und GPX4-Promotorkonstrukten. Um die Wirkungen von AG auf die Selenoprotein-Translation besser zu verstehen, wurden die SECIS-Elemente von GPX1-, GPX4- und SEPP-Transkripten in ein Reportersystem kloniert und auf eine Regulation durch AG und Se analysiert. Die Ergebnisse zeigen, dass der korrekte Se-Einbau vom Se-Status, von der AG-Konzentration und dem spezifischen SECIS-Element abhängig ist. Auf transkriptionaler und translationaler Ebene führten AG zu stark erhöhten SEPP-Spiegeln, während die Expression und Enzymaktivität von GPX und DIO1 nur in geringerem Ausmaß beeinflusst wurden. Eine Analyse der Se-Beladung zeigte, dass der Se-Gehalt von SEPP stark durch AG reduziert und vom Se-Status abhängig war.
Selenoproteins play important roles in antioxidant defence and immunoregulation. Selenium (Se) metabolism is controlled by hepatocytes synthesizing and secreting the Se-transporter selenoprotein P (SEPP) declining in critical illness, e.g., sepsis. Sepsis triggers excessive production of pro-inflammatory cytokines. Aminoglycoside (AG) antibiotics applied in sepsis in induce mRNA misinterpretation including the stop codon UGA required during selenoproteins biosynthesis. The molecular interplay between the cytokines IL-6, IL-1b and TNFa, AG and Se-status on selenoprotein expression was investigated in hepatic-derived cell lines. IL-6 strongly reduced the level of SEPP mRNA and secreted SEPP in a dose-dependent manner. Likewise, expression of selenoenzyme type 1 deiodinase (DIO1) declined at the transcript, protein and enzyme activity level. The effects of IL-6 on the expression of antioxidative-acting glutathione peroxidases (GPX) were isozyme-specific; while transcript level of GPX2 increased and those of GPX4 decreased, GPX1 remained unaffected. IL-6-dependent effects were reflected in reporter gene experiments of selenoprotein promoter constructs. Characterising the effects of AG on selenoprotein translation, the SECIS-elements of GPX1, GPX4 and SEPP transcripts were cloned into a reporter system and analysed for their response to AG and Se. The results indicate that the correct co-translational Se-insertion depends on the Se-status, AG concentration and the specific SECIS-element. At both transcriptional and translational levels, SEPP levels were strongly increased in response to AG, whereas the expression and enzyme activity of GPX and DIO1 were affected to a lower degree. Analysis Se-status indicate that the Se-content of SEPP was strongly reduced by AG and depends on Se-status.

This thesis focuses on development of web-based GPS data management system in a cloud environment. The thesis introduces the most used application interfaces for building custom mapping applications. It offers a comparison of cloud platforms such as Google App Engine and OpenShift Online. It also deals with the design and the implementation of system for OpenShift Online platform. The system focuses on importing tracks from GPX format, managing tracks, viewing tracks on map tiles from Mapy.cz, searching for tracks, creating an elevation profile and various statistics.

Des études menées sur des modèles animaux ont montré que le métabolisme oxydatif joue un rôle important dans l’hématopoïèse normale et leucémique via le contrôle de l’activation de p38 MAPK. Nous avons établi que les cellules CD34+CD38- médullaires humaines ont un très faible niveau d’H2O2 et une forte expression de GPX3, le gène codant l’enzyme antioxydante glutathion peroxydase-3 (GPx-3), un déterminant majeur du potentiel souche des cellules hématopoïétiques. De plus, la niche leucémique étant essentielle pour l’auto-renouvellement des cellules souches leucémiques, nous avons étudié, chez l’homme, le rôle des cellules souches/stromales mésenchymateuses (CSM) médullaires primaires, dans la régulation de l’axe GPx-3/H2O2/p38 MAPK des cellules leucémiques et avons montré que les CSM contrôlent cet axe dans les cellules leucémiques humaines KG1a en régulant l’expression de GPx-3. Ces résultats ont bénéficié du développement de deux méthodes originales, l’une quantifiant l’expression des gènes antioxydants par RT-qPCR (« antioxydogramme », brevet) et l’autre permettant une analyse en haute résolution du cycle cellulaire par cytométrie en flux
Studies in animal models have demonstrated that oxidative metabolism plays an important role in normal and leukemic hematopoiesis by controlling the p38 MAPK activation. We have established that the human bone marrow CD34+CD38- cells have a very low H2O2 level and express GPX3, the gene encoding for the antioxidative enzyme gluthathione peroxidase-3 (GPx-3) which is a major determinant of the stem cell potential of hematopoietic cells. As the niche is essential for the leukemic stem cell self-renewal, we have studied the role of human primary bone marrow mesenchymal stromal/stem cells (MSCs) in regulating the axis GPx-3/H2O2/p38 MAPK in human leukemic cells and we have shown that MSCs control this axis in human KG1a leukemic cells by regulating the expression of GPx-3. These results benefited from the development of two original methods, the first one quantifying the expression of by RT-qPCR of antioxidative genes (“antioxidogram”, patent) and the second one for high resolution analysis of the cell cycle by flow cytometry

This master's thesis practical goal is to create an application with usefull graphical users interface, which allows to import training data from GPS device. Also it will generate graphical and statistical outputs of achived results with export option to HTML and tabular processors format. Theoretical part of this thesis presents introduction to creating of a training diary, short description of GPS system function, as next it describes GPS data storage formats and application design.

Affecting 5-7% of all pregnancies, pre-eclampsia is a dangerous complication of pregnancy which poses a serious health risk to both mother and fetus. It is a major cause of maternal and perinatal morbidity and is characterised by hypertension, proteinuria, edema and platelet aggregation. Despite the severity of the disease, no comprehensive theory has been determined to explain the pathogenesis of the disease, with delivery being the only curative treatment of this multisystem disorder of pregnancy. Oxidative stress plays a crucial role in the pathogenesis of pre-eclampsia, which results in placental injury causing a hypoxic environment and eventually levels of anti-oxidants are markedly decreased. This leads to the activation of cell death pathways such as apoptosis and necrosis. The findings reported in this thesis suggest that selenium supplementation could be a potential therapy for treating women who are at risk of developing pre-eclampsia. In this study, selenium supplementation was used to up-regulate the expression of endogenous anti-oxidants, Glutathione Peroxidase (GPx) and Thioredoxin-Reductase (Thx-Red). It has been well documented in the literature that pre-eclampsia is caused by oxidative stress and in an attempt to address this we investigated whether oxidative stress in trophoblast-like cells is protected by selenium supplementation. Trophoblast-like cells, BeWo, JEG-3 and Swan-71 cells were exposed to endogenous stressors such as Rotenone and Antimycin which are able to generate mitochondrial oxidative stress by inhibiting the electron transport chain.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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The work deals with recording and tracking of the objects in a certain area. It also puts mind to web services, mapping applications and modern standards, which seeks to compare and choose the best for this project. Then explore the existing systems and discusses their pros and cons, which specifies the requirements and propose solutions to information system built of selected technologies in order to create a friendly user interface. The proposed solution implements using modern PHP frameworks based on the MVP design pattern, and finally deals with verification of functionality and outline future developments.

This work describes a relatively new technique designed to write highly parallel programs, that name is OpenCL. It is intended for both GPU and CPU and other parallel processors. Libraries used by the processor architecture, which includes a large number of small cores. These cores are not as comprehensive as conventional processors and is therefore suitable for calculations, which are many and they are simple. It is this property could, under certain conditions, accelerate the calculation of the hologram, namely the calculation of the optical field. While the calculation itself is simple, but the amount of processed data is large and therefore slow. The work also contain the basic concepts of explanation of optical and digital holography.

This diploma thesis is focused on object detections through general-purpose computing on graphics processor units. There is an explanation of graphics adapters work and basics of their architecture in this thesis. Based on the adapters, there is the effective work in libraries for general-purpose computing on graphics processor units demonstrated in this thesis. Further, the thesis shows the available algorithms for object detection and which ones from them are possible to be effectively parallelized. In conclusion of this thesis, there is a comparison of the object detections speeds to common implementations on classical processors.

This thesis explores the design and experimental implementation of GPF, a novel protocol-independent, multi-match packet classification framework. This framework is targeted and optimised for flexible, efficient execution on NVIDIA GPU platforms through the CUDA API, but should not be difficult to port to other platforms, such as OpenCL, in the future. GPF was conceived and developed in order to accelerate classification of large packet capture files, such as those collected by Network Telescopes. It uses a multiphase SIMD classification process which exploits both the parallelism of packet sets and the redundancy in filter programs, in order to classify packet captures against multiple filters at extremely high rates. The resultant framework - comprised of classification, compilation and buffering components - efficiently leverages GPU resources to classify arbitrary protocols, and return multiple filter results for each packet. The classification functions described were verified and evaluated by testing an experimental prototype implementation against several filter programs, of varying complexity, on devices from three GPU platform generations. In addition to the significant speedup achieved in processing results, analysis indicates that the prototype classification functions perform predictably, and scale linearly with respect to both packet count and filter complexity. Furthermore, classification throughput (packets/s) remained essentially constant regardless of the underlying packet data, and thus the effective data rate when classifying a particular filter was heavily influenced by the average size of packets in the processed capture. For example: in the trivial case of classifying all IPv4 packets ranging in size from 70 bytes to 1KB, the observed data rate achieved by the GPU classification kernels ranged from 60Gbps to 900Gbps on a GTX 275, and from 220Gbps to 3.3Tbps on a GTX 480. In the less trivial case of identifying all ARP, TCP, UDP and ICMP packets for both IPv4 and IPv6 protocols, the effective data rates ranged from 15Gbps to 220Gbps (GTX 275), and from 50Gbps to 740Gbps (GTX 480), for 70B and 1KB packets respectively.
LaTeX with hyperref package

Abstract About one-third of mammalian proteins are secreted proteins and membrane proteins. Most of these proteins contain disulfide bonds in their native state, covalent links formed between the thiol groups of cysteine residues. In many proteins, disulfide bonds play an essential role in folding, stabilizing structure and the function of the protein. Therefore, understanding the pathways of disulfide bond formation is crucial for a wide range of medical processes and therapies. Disulfide bond formation is catalyzed by the Protein Disulfide Isomerase (PDI) family. To date the mechanisms of the PDIs in disulfide bond formation and pathways for disulfide bond formation have not been fully characterized. Here the structure of the substrate binding b’x domain of human PDI was determined. The structure shows that the b' domain has a typical thioredoxin fold and that the x region can interact with the substrate binding site of the b' domain. Specifically, the x region of PDI can adopt alternative conformations during the functional cycle of PDI action and that these are linked to the ability of PDI to interact with folding substrates. In addition, this study showed that two human proteins, GPx7 and GPx8 are involved in disulfide bond formation. The addition of GPx7 or GPx8 to a folding protein along with PDI and peroxide allows the efficient oxidative refolding of a reduced denatured substrate protein. Finally, this thesis includes the development of a system for the efficient production of disulfide bond containing proteins in the cytoplasm of E. coli. It showed that the introduction of Erv1p, a sulfhydryl oxidase and FAD-dependent catalyst of disulfide bond, allows the formation of native disulfide bonds in the cytoplasm of E. coli even without the disruption of genes involved in disulfide bond reduction. Introduction of Erv1p and a disulfide isomerase, e.g. PDI, allows the efficient formation of natively folded eukaryotic proteins with multiple disulfide bonds in the cytoplasm of E. coli. This system is able to express high levels of complex disulfide bonded eukaryotic proteins
Tiivistelmä Noin kolmasosa kaikista nisäkkäiden proteiineista on solun ulkopuolelle eritettäviä proteiineja ja kalvoproteiineja. Monet näistä proteiineista sisältävät natiivissa konformaatiossaan disulfidisidoksia, jotka ovat kovalenttisia sidoksia kysteiinitähteiden tioliryhmien välillä. Useissa proteiineissa näillä disulfidisidoksilla on keskeinen rooli proteiinin laskostumisessa, kolmiulotteisen rakenteen stabiloinnissa sekä proteiinin toiminnassa. Disulfidisidosten muodostumisen taustalla olevien mekanismien tunteminen onkin tärkeää monien lääketieteellisten prosessien ja hoitomenetelmien kannalta. Disulfidisidosten muodostumista katalysoivat proteiinidisulfidi-isomeraasi (PDI) -perheeseen kuuluvat entsyymit. PDI entsyymien toimintamekanismeja ja disulfidisidosten muodostumisen reaktioreittejä ei kuitenkaan vielä tunneta tarkasti. Tässä väitöskirjassa selvitettiin ihmisen PDI entsyymin substraattia sitovan b’x alayksikön rakenne. Rakenteesta voidaan todeta b’ alayksikön laskostuminen tyypilliseen tioredoksiini muotoon sekä x alueen interaktio b’ alayksikön substraattia sitovan kohdan kanssa. PDI entsyymin katalysoiman reaktioketjun aikana x alayksikkö voi muuttaa konformaatiotaan mahdollistaen PDI entsyymin interaktion laskostuvien substraattiproteiinien kanssa. Tässä tutkimuksessa osoitettiin myös kahden ihmisen proteiinin, GPx7 ja GPx8 osallistuminen disulfidisidosten muodostumista katalysoiviin reaktioihin. GPx7 ja GPx8 entsyymien lisäys laskostumisreaktioon yhdessä PDI:n ja vetyperoksidin kanssa mahdollistaa pelkistetyn, denaturoidun substraattiproteiinin tehokkaan, hapettaviin reaktioihin perustuvan uudelleenlaskostumisen natiiviin muotoonsa. Osana tätä väitöstutkimusta kehitettiin menetelmä, joka mahdollistaa disulfideja sisältävien proteiinien tehokkaan tuoton E.colin solulimassa. Menetelmässä sulfhydryylioksidaasina ja FAD:sta riippuvana disulfidisidosten muodostumisen katalysaattorina toimiva Erv1p mahdollistaa disulfidisidosten muodostumisen E.colin solulimassa myös ilman solun pelkistävien reaktioreittien geneettistä poistamista. Erv1p yhdessä disulfidi-isomeraasin, kuten PDI, kanssa mahdollistaa oikein laskostuneiden, useita disulfidisidoksia sisältävien eukaryoottisten proteiinien tehokkaan tuotannon E.colin solulimassa. Menetelmällä pystytään tuottamaan suuria määriä monimutkaisia disulfidisidoksellisia proteiineja

Cette thèse est centrée sur l'affichage et la manipulation en temps interactif au sein d'un navigateur Internet de modèles 3D issus de Systèmes d'Informations Géographiques (SIG). Ses principales contributions sont la visualisation de terrains 3D haute résolution, la simplification de maillages irréguliers sur GPU, et la création d'une nouvelle API navigateur permettant de réaliser des traitements lourds et efficaces (parallélisme GP/GPU) sans compromettre la sécurité. La première approche proposée pour la visualisation de modèles de terrain s'appuie sur les récents efforts des navigateurs pour devenir une plateforme versatile. Grâce aux nouvelles API 3D sans plugin, nous avons pu créer un client de visualisation de terrains "streamés" à travers HTTP. Celui-ci s'intègre parfaitement dans les écosystèmes Web-SIG actuels (desktop et mobile) par l'utilisation des protocoles standards du domaine (fournis par l'OGC, Open Geospatial Consortium). Ce prototype s'inscrit dans le cadre des partenariats industriels entre ATOS Worldline et ses clients SIG, et notamment l'IGN (institut national de l'information géographique et forestière) avec le Géoportail (http://www.geoportail.gouv.fr) et ses API cartographiques. La 3D dans les navigateurs possède ses propres défis, qui sont différents de ce que l'on connaît des applications lourdes : aux problèmes de transfert de données s'ajoutent les restrictions et contraintes du JavaScript. Ces contraintes, détaillées dans le paragraphe suivant, nous ont poussé à repenser les algorithmes de référence de visualisation de terrain afin de prendre en compte les spécificités dues aux navigateurs. Ainsi, nous avons su profiter de la latence du réseau pour gérer dynamiquement les liaisons entre les parties du maillage sans impacter significativement la vitesse du rendu. Au-delà de la visualisation 3D, et bien que le langage JavaScript autorise le parallélisme de tâches, le parallélisme de données reste quasi inexistant au sein des navigateurs Web. Ce constat, couplé à la faiblesse de traitement du JavaScript, constituait un frein majeur dans notre objectif de définir une plateforme SIG complète et performante intégrée au navigateur. C'est pour cette raison que nous avons conçu et développé, à travers les WebCLWorkers, une API Web de calcul GP/GPU haute performance répondant aux critères de simplicité et de sécurité inhérents au Web. Contrairement à l'existant, qui se base sur des codes déjà précompilés ou met de côté les performances, nous avons tenté de trouver le bon compromis pour avoir un langage proche du script mais sécurisé et performant, en utilisant les API OpenCL comme moteur d'exécution. Notre proposition d'API a intéressé la fondation Mozilla qui nous a ensuite demandé de participer à l'élaboration du standard WebCL dans la cadre du groupe Khronos, (aux côtés de Mozilla mais aussi de Samsung, Nokia, Google, AMD, etc.). Grâce aux nouvelles ressources de calcul ainsi obtenues, nous avons alors proposé un algorithme de simplification parallèle de maillages irréguliers. Alors que l'état de l'art repose essentiellement sur des grilles régulières pour le parallélisme (hors Web) ou sur la simplification via clusterisation et kd-tree, aucune solution ne permettait d'avoir à la fois une simplification parallèle et des modèles intermédiaires utilisables pour la visualisation progressive en utilisant des grilles irrégulières. Notre solution repose sur un algorithme en trois étapes utilisant des priorités implicites et des minima locaux afin de réaliser la simplification, et dont le degré de parallélisme est linéairement lié au nombre de points et de triangles du maillage à traiter [etc...]GP/GPU
This thesis focuses on displaying and manipulating 3D models from Geographic Information Systems (GIS) in interactive time directly in a web browser. Its main contributions are the visualization of high resolution 3D terrains, the simplification of irregular meshes on the GPU, and the creation of a new API for performing heavy and effective computing in the browser (parallelism GP/GPU) without compromising safety. The first approach proposed for the visualization of terrain models is built on recent browsers efforts to become a versatile platform. With the new 3D pluginless APIs, we have created a visualization client for terrain models “streamed” through HTTP. It fits perfectly into the current Web-GIS ecosystem (desktop and mobile) by the use of the standard protocols provided by OGC Open Geospatial Consortium. This prototype is part of an industrial partnership between ATOS Wordline and its GIS customer, and particularly the IGN (French National Geographic Institute) with the Geoportail application (http://www.geoportail.gouv.fr) and its mapping APIs. The 3D embedded in browsers brings its own challenges which are different from what we know in heavy applications: restrictions and constraints from JavaScript but also problems of data transfer. These constraints, detailed in the next paragraph, led us to rethink the standard algorithms for 3D visualization to take into account the browser specificities. Thus, we have taken advantage of network latency to dynamically manage the connections between the different parts of the mesh without significantly impacting the rendering speed. Beyond 3D visualization, and even if the JavaScript language allows task parallelism, data parallelism remains absent from Web browsers. This observation, added to the slowness of JavaScript processing, constituted a major obstacle in our goal to define a complete and powerful GIS platform integrated in the browser. That is why we have designed and developed the WebCLWorkers, a GP/GPU Web API for high performance computing that meets the criteria of simplicity and security inherent to the Web. We tried to find a trade-off for a language close to the script but secure and efficient, based on the OpenCL API at runtime. This approach is opposite to the existing ones, which are either based on precompiled code or disregard performances. Our API proposal interested the Mozilla Foundation which asked us to participate in the development of the WebCL standard by integrating the Khronos Group (Mozilla, Samsung, Nokia, Google, AMD, and so on). Exploiting these new computing resources, we then suggested an algorithm for parallel simplification of irregular meshes. While the state of the art was mainly based on regular grids for parallelism (and did not take into account Web browsers restrictions) or on simplification and kd-tree clustering, no solution could allow both parallel simplification and progressive visualization using irregular grids. Our solution is based on a three-step algorithm using implicit priorities and local minima to achieve simplification, and its degree of parallelism is linearly related to the number of points and triangles in the mesh to process. We have proposed in the thesis an innovative approach for 3D WebGIS pluglinless visualization, offering tools that bring to the browser a comfortable GP/GPU computing power, and designing a method for irregular meshes parallel simplification allowing to visualize level of details directly in Web browsers. Based on these initial results, it becomes possible to carry all the rich functionalities of desktop GIS clients to Web browsers, on PC as well as mobile phones and tablets

Location-based services have grown in importance as smartphones, and location-based applications have become an integral part of everyday life. While Global Navigation Satellite Systems (GNSSs) provide the most accurate position determination, open service GNSS signals remain unprotected and susceptible to spoofing attacks. Previous work within the domain highlighted this issue, with many smartphone receivers shown susceptible to GPS L1 spoofing, suggesting that their resilience experiments should be extended to include other GNSS signals in the future. Given that multi-GNSS receivers now have become the norm in smartphones, this thesis investigates whether smartphone GNSS receiver spoofing resilience depends on the type of signal; by conducting a series of comparative spoofing experiments involving GPS L1 and Galileo E1-B/C signals. To conduct the experiments, we developed a Galileo E1-B/C signal simulator that, together with the open-source GPS-SDR-SIM signal simulator, was the basis for conducting a series of experiments designed to identify the potential presence of anti-spoofing measures. The result of our experiments indicates that smartphone multi-GNSS receivers were significantly more resilient towards Galileo E1-B/C spoofing attacks, often accepting GPS L1 signals with significant position, time, and data errors, while refusing to accept corresponding Galileo E1-B/C signals. While we never observed cases of E1-B/C signals being accepted while rejecting GPS L1 signals, external factors limited the scope of the investigation and do not allow a generalized conclusion. As such, to deepen our understanding of these issues and how they relate to the development of anti-spoofing measures and trust in different signals, it is essential to extend this research to include more devices and other GNSS signals.
Positionstjänster har växt i betydelse allteftersom smarttelefoner och positionsapplikationer har blivit en integral del av våran vardag. Även om satellitpositionering utger det mest precisa och vedertagna positionsbestämningen av tillgängliga positionstjänser så är de publika satellitnavigeringssignalarna oskyddade och sårbara för förfalskningsattacker. Tidigare forskning inom området har evaluerat dessa sårbarheter och visat att ett betydande antal smarttelefoner var sårbara för GPS-L1 förfalskningsattacker och att denna forskning borde utökas i framtiden allteftersom satellitnavigeringsmottagare med förmåga att mottaga olika satellitsignaler integreras i smarttelefoner. Givet att en majoritet av nya smarttelefoner nu integrerar denna typ av mottagare så utvärderar detta arbete hur sårbarheten mot förfalskningsattacker beror på typ av satellitsignal genom en komparativ jämförelse av sårbarhet mellan GPS-L1 och den nyare Galileo E1-B/C signalen. För att genomföra utvärderingen så utvecklade vi en Galileo E1-B/C signalsimulator som tillsammans med GPS-L1 signalsimulatorn (GPS-SDR-SIM) utgjorde grunden för en serie av experiment designade för att identifiera och utvärdera sårbarheter och potentiella motåtgärder i smarttelefoner. Våra resultat indikerar att smarttelefoner är betydligt mer sårbara for GPS-L1 forfalskningsattacker då de accepterade GPS-L1 signaler med betydande position, tid, och datafel medans motsvarande Galileo E1-B/C signaler ej accepterades. Trots resultaten så är det viktigt att inte dra för starka slutsatser då underlaget var kraftigt begränsat givet rådande omständigheter (Covid), som gjorde det svårt/omöjligt att på ett säkert sätt samla volontärer med olika smarttelefoner för våra experiment. Därav så är det viktigt att i framtiden utöka arbetet med ett större underlag och fler signaltyper.

Les glycophorines a (gpa) et b (gpb) sont les sialoglycoproteines majeures de la membrane du globule rouge. Elles portent respectivement les antigenes de groupe sanguin mn et ss. Nous avons etudie la structure des genes gpa et gpb, et mis en evidence un troisieme gene, gpe, membre de la meme famille. Les trois genes sont organises dans le sens 5 gpa-gpb-gpe 3, et definissent le locus gyp situe sur le chromosome 4, en position q28-31. Les genes sont extremement homologues entre eux, sauf pour les parties 3 non-codantes des genes gpb et gpe qui divergent completement de la sequence 3 non-codante du gene gpa. Cette divergence est due a une recombinaison entre des sequences alu apres duplication du gene gpa ancestral. Nous avons clone et analyse les sequences promotrices des trois genes sur 350 nt en amont du site d'initiation de la transcription, et montre qu'elles ne presentent que quelques mutations ponctuelles les unes par rapport aux autres. Nous avons mis en evidence que ces divergences n'influaient pas sur les taux de transcription des trois genes tout-a-fait comparables entre eux. Par contre, nous avons montre que des differences de stabilite des arn messagers correspondant aux trois genes peuvent rendre compte des differents taux d'arnm et des differences d'expression des glycophorines abe sur la membrane erythrocytaire. Nous avons analyse de maniere detaillee le promoteur gpb, et mis en evidence les sequences en cis, et les facteurs en trans impliques dans l'initiation de la transcription, le niveau d'expression et la specificite erythroide de l'expression du gene. Cette derniere analyse nous a permis de definir un modele de regulation, ou un represseur inhibe la transcription du gene dans les tissus non erythroides, et ou hgata-1, un facteur erythroide, deplace le facteur inhibiteur par competition et leve ainsi la repression dans les tissus erythroides.

Gli ultimi anni hanno visto un incremento rilevante nella diffusione e utilizzo delle General Purpose Graphics Processing Unit (GP-GPU), unità di elaborazione grafica ad elevate performance. Tale diffusione è principalmente dovuta al vantaggioso rapporto tra la capacità computazione offerta da questi device ed il loro costo. Molto diffusi sono anche i problemi con sistemi lineari di grandi dimensioni, specialmente in ambito scientifico, e richiedono grandi capacità di calcolo per essere risolti in tempi brevi. Grazie alle loro performance computazionali le GP-GPU possono essere usate per velocizzare la soluzione di questi sistemi. In questo trattato si vuole sviluppare algoritmi per la soluzione di sistemi lineari che lavorino su Graphics Processing Unit (GPU) e sperimentarne le performance confrontandole con algoritmi preesistenti. L’obbiettivo è la realizzazione di soluzioni per applicazioni High Performance Computing (HPC) in grado di avvantaggiarsi significativamente della potenza di calcolo aggiuntiva fornita dalle GPU cosicché riescano ad ottenere miglioramenti significativi in termini di performance rispetto alle tradizionali applicazioni per CPU in problemi applicativi reali: la soluzione di piccoli e grandi sistemi lineari. La tesi proposta è incentrata sull’implementazione di algoritmi basati sull’Inhibition Method. La tecnologia utilizzata per lo sviluppo e il testing delle implementazioni è la Compute Unified Device Architecture (CUDA), attualmente la tecnologia maggiormente impiegata da chi lavora nell’ambito GP-GPU. In particolare, mostrerò il funzionamento di CUDA, i suoi punti di forza e di debolezza e come poter trarre vantaggio dal suo utilizzo nonché le strategie che conviene adottare per impiegarne al meglio le risorse e sfruttare al massimo le capacità. Presenterò dunque diverse implementazioni di algoritmi per la soluzione di sistemi lineari in svariate versioni e le confronterò con lo stato dell’arte per verificarne la validità.

Actualmente se han desarrollado trabajos sobre la criopreservación de espermatozoides epididimarios de alpaca, demostrando disminución en los parámetros de viabilidad, motilidad e integridad de la membrana plasmática luego del proceso de descongelación, debido principalmente a especies de oxígeno reactivas producidas durante el proceso de congelamiento. El objetivo de este estudio fue evaluar el efecto de la criopreservación sobre las proteínas antioxidantes GPX1 y GPX4 de espermatozoides del epidídimo de alpaca, usamos muestras (n: 30) de espermatozoides provenientes de la cola del epidídimo, se usó un método de congelamiento lento usando dimetilacetamida (0,375 M) como agente crioprotector, analizamos los parámetros de la motilidad, viabilidad e integridad de la membrana plasmática antes y después del proceso de congelamiento; así mismo evaluamos los extractos de proteínas de espermatozoides antes y después del congelamiento para evaluar el estado de estas proteínas mediante Western blott, la evaluación de la localización intracelular de estas proteínas se realizó mediante la técnica de inmunofluorescencia. Se usó la técnica de RT-PCR-RT para evaluar el nivel de expresión del gen GPX4 en biopsias de tejido testicular. Los resultados mostraron una disminución en los porcentajes de los parámetros de viabilidad, motilidad e integridad de la membrana plasmática luego del proceso de congelamiento, la localización intracelular de las proteínas GPx1 (cabeza del espermatozoide) y GPx4 (flagelo del espermatozoide) muestran los principales lugares de acción de estas proteínas, por Western blot obtuvimos bandas de peso molecular variado para GPx1 (formas inactivas de la proteína) y bandas de peso molecular de 27kDa para GPx4 (forma activa); obtuvimos una relación significativa positiva y débil entre el nivel de expresión molecular del gen GPx4 y la motilidad pre y post congelamiento. La ubicación de las proteínas GPx1 y GPx4 demuestra sus funciones de protección del espermatozoide de alpaca, la cual no se vio afectada por el proceso de criopreservación, pero el estado (forma activa) de la proteína GPx1 si se vio afectada. Existe una relación positiva significativa (p<0.01) entre el nivel de expresión relativa del gen GPx4 respecto a la movilidad espermática. Palabras clave: Alpaca, criopreservación, espermatozoides, glutatión peroxidasa
--- Currently works about cryopreservation of epididymal alpaca sperm have been developed, showing decrease of the parameters of viability, motility and plasma membrane integrity after thawing process, mainly due to reactive oxygen species produced during cooling process. The aim of this study was to evaluate the effect of cryopreservation over the antioxidant proteins GPx1 and GPx4 from epididymal alpaca sperm. We used samples (n:30) of sperm obtained from the cauda of epididymis, and a slow freezing process with dimethylacetamide (0.375M) as a cryoprotectant agent. It was analyzed the parameters of motility, viability and integrity of plasma membrane before and after cooling process; the protein extracts from sperm was evaluated before and after cooling to examine the state of this protein by western blott technique; the intracellular localization of this proteins was done by immunofluorescence technique, the expression level of gene Gpx4 in testicular tissue biopsies was quantified by RT-PCR-RT. The results showed a decrease in the percentage of viability, motility and plasma membrane integrity after thawing process; the intracellular localization of GPx1 and GPx4 were identified in regions such as the head (GPx1) and flagellum (GPx4) of sperm, by western blot we got bands of GPx1 inactive forms of the protein and the active form of GPx4 (27 kDa); It was obtained a significant positive relationship between the level of molecular gene expression of GPx4 and motility before and after cooling process The location of proteins GPx1 and GPx4 demonstrate its functions of protection of alpaca sperm, which was not altered by the cryopreservation process, but the state (active form) of protein GPx1 was affected. There is a positive weak correlation between the level of GPx4 gene relative expression with sperm motility. Key words: Alpaca, cryopreservation, spermatozoa, glutation peroxidase.
Tesis

Thesis (M.A.)--University of Utah, 1976.
Includes bibliographical references (p. 268-271). Also available via Internet from the Marines web site. Address as of 7/30/08: http://www.marines.mil/news/publications/Documents/ALLIGATORS,%20BUFFALOES,%20AND%20BUSHMASTERS%20%20PCN%2019000319000.pdf; current access available via PURL.

The global Positioning System (GPS) provides location and time information as long as there are unobstructed lines of sight to four or more GPS satellites. However, when this is not the case the signal may be inaccurate or sometimes even completely blocked. In these situations the Inertial Navigation System (INS) is an appropriate choice for positioning.  An INS has already been proposed in a previous thesis by Erik Andersson and the objective of this thesis is to fuse the GPS with the INS in a proper way. A part of this project is to decide the reliability of the GPS.Three methods for GPS reliability detection have been proposed. One method based on the statistical properties of each of the separate systems, and two methods based on the statistical properties of the residuals between the GPS and INS. Two methods for GPS/INS integration have been proposed. One method based on a bank of parallel running Kalman filters and one method based on an adaptive observer.The method based on Kalman filter diverged. By adding a state that was suppose to represent the bias of the noise an attempt was to fix this problem made. The filter still diverged and was not examined any further. Among the other two algorithms did the one that uses both magnetometer and gyroscope presents a better result than the one that uses only gyroscope. However, the result differences between the two algorithms were not big and the result may change if a better INS is used.

Розроблено структурну схему GPS приймача, на основі якої розроблено схему електричну принципову. Проведено розрахунок схеми електричної принципової приладу. Розроблено друковану плату та друкований вузол. Основні техніко-експлуатаційні характеристики: тип приймача – 12 паралельних каналів L1 C/A код, точність визначення місцеположення – 5 м, повторне захоплення сигналу – через 1 сек, чутливість – 137-145дБм, протокол – NMEA-0183, версія 3.01 9600 бод, 8N1, напруга живлення – 12-15 В, можливість підключення до ПК – через Com-порт
The structural scheme of the GPS receiver is developed, on the basis of which the electric basic scheme is developed. The calculation of the scheme of the electric principle device is carried out. A printed circuit board and a printed circuit board have been developed. Main technical and operational characteristics: type of receiver - 12 parallel channels L1 C / A code, accuracy of positioning - 5 m, re-capture of the signal - after 1 sec, sensitivity - 137-145dBm, protocol - NMEA-0183, version 3.01 9600 baud, 8N1, supply voltage - 12-15 V, the ability to connect to a PC - via Com-port.
Перелік умовних позначень, символів, одиниць, скорочень і термінів 6 Вступ 7 1 Основна частина 8 1.1 Аналіз технічного завдання 8 1.1.1 Обґрунтування актуальності теми дипломного проекту 8 1.1.2 Аналіз інформації 14 1.2 Розробка структурної схеми пристрою 14 1.3 Проектування і розрахунок вузлів електричної принципової схеми пристрою 16 1.4 Вибір і обґрунтування компонентної бази 22 1.5 Компоновка друкованого вузла пристрою 29 1.5.1 Розробка компоновки і конструкції друкованого вузла 29 1.5.2 Оптимізація компоновки, друкованого вузла 34 1.5.3 Розрахунок і забезпечення вимог по надійності 40 1.6 Висновок до розділу 1 45 2 Охорона праці та безпека життєдіяльності 46 2.1 Вплив шуму на організм людини та розробка заходів щодо його зниженню до допустимих величин 46 2.2 Організація управління ЦЗ та реагування на НС на підприємстві (цеху) відповідного профілю 50 2.3 Висновок до розділу 2 51 Висновки 52 Список використаних джерел 53 Додатки 55

Мета роботи – спроектувати та сконструювати макет GPS – трекера. Отримати дані про місце знаходження приладу. В дипломному проекті: - розглянуто існуючі глобальні навігаційні супутникові системи; - методи позиціювання об’єктів у просторі; - наведені характеристики використаємо апаратури; - приведено алгоритм роботи пристроїв позиціювання; - наведені характеристики існуючих трекерів; - розроблено корпус макету пристрою; - виготовлено корпус макету пристрою; - проведено випробування приладу; Основою трекера було обрано GPS – модуль Ublox Neo 7m та плату Arduino nano 328 p.
Theme of the diploma project: "GPS - tracker". The diploma project consists of an explanatory note - 52 pages, drawings A1 - 1, posters A2 - 2. Number of sources by the list of references - 9. The purpose of the work is to design and construct a GPS tracker layout. Get the location of the device. In the diploma project: - Existing global satellite navigation systems are considered; - methods of positioning objects in space; - the above characteristics we use the equipment; - the algorithm of the positioning devices is shown; - characteristics of existing trackers are given; - The case layout of the device is developed; - the case of the layout of the device is made; - test of the device; The basis of the tracker was chosen GPS - the module Ublox Neo 7m and board Arduino nano 328 p.

This master’s thesis is the design of the system of the differential GPS, creation of the software for basic wireless communication between 2 GPS receivers, and practical tests of the designed system. Parameters and characteristics of system were determined and they should inform us better about the appropriateness of the designed system for navigation of a mobile robot in outside conditions.

Från den 1 april 2006 har SWEPOS kompletterat den befintliga nätverks-RTK-tjänsten, som dittills levererat RTK-data för GPS, med ett alternativ där RTK-data för GPS/GLONASS levereras. En del användare har rapporterat att de upplever att GPS/GLONASS inte tillför något och även att det ibland kan ta längre tid att få fixlösning. Andra användare hävdar att de nu kan använda nätverks-RTK på platser där de tidigare inte kunde mäta och är mycket positiva till GPS/GLONASS.

Syftet med detta examensarbete var att undersöka hur tillgängligheten för satellitmätning, positionsnoggrannheten och initialiseringstiden påverkades i öppna respektive störda miljöer med GPS/GLONASS jämfört med enbart GPS vid användandet av nätverks-RTK-tjänsten. Undersökningen har utförts med tre olika fabrikat av GNSS-mottagare (Leica, Topcon och Trimble), vilket även medger att en jämförelse mellan dessa till viss utsträckning kan göras.

I studien gjordes totalt 1 440 mätningar på sex punkter med kända positioner och med olika grad av sikthinder. Fixlösning uppnåddes inte inom 180 sekunder för 206 (77 för GPS/GLONASS och 129 för GPS) av de 1 440 mätningarna.

De extra GLONASS-satelliterna tillför en klar fördel när det gäller möjligheten att mäta i störda miljöer. När det gäller initialiseringstid så är dessa kortare för GPS/GLONASS. GLONASS-satelliterna ger ingen förbättring av positionsnoggrannheten. Det är till och med så att GPS får något bättre kvalitetstal i både plan och höjd i denna studie (1-3 mm bättre). För de olika fabrikaten kan det konstateras att precision och noggrannhet är likvärdiga i både plan och höjd för alla tre märken.

On the 1st of April 2006, SWEPOS complemented the existing network RTK service with corrections for the Russian satellite system GLONASS. The service had so far only provided corrections for GPS. Some users have claimed that GPS/GLONASS do not contribute at all and also that the time for initialization sometimes can be longer. However, other users insist on that they now can use network RTK in areas that earlier were impossible and they are very favourable of GPS/GLONASS.

The purposes of this diploma work were to study and examine measurements using GPS and GPS/GLONASS in areas with different degrees of visual obstacles. Corrections were provided by SWEPOS Network RTK service and availability of satellites, accuracy of position and time for initialization were evaluated. The study has been conducted with three different brands of GNSS receivers (Leica, Topcon and Trimble), which also to some extent makes a comparison between the three brands possible.

A total number of 1 440 field measurements were made on six well-known points with different degrees of visual obstacles. A fixed solution was not accomplished within 180 seconds for 206 (77 for GPS/GLONASS and 129 for GPS) of the 1 440 measurements.

The additional GLONASS satellites provide an apparent advantage regarding the possibility to measure in disturbed environments. The time for initialization is shorter for GPS/GLONASS. The GLONASS satellites do not give any improvement in accuracy of position. On the contrary, GPS receives slightly better accuracy numbers in quality for both horizontal and vertical readings (1-3 mm better). Regarding the different brands, it was found that the precision and accuracy were similar in both plane and height for all three brands.

Networking technology is connecting more and more people around the world. It has become an essential part of our daily life. For this connectivity to be seamless, networks need to be fast. Nonetheless, rapid growth in network traffic and variety of communication protocols overwhelms the Central Processing Units (CPUs) processing packets in the networks. Existing solutions to this problem such as ASIC, FPGA, NPU, and TOE are not cost effective and easy to manage because they require special hardware and custom configurations. This thesis approaches the problem differently by offloading the network processing to off-the-shelf Graphic Processing Units (GPUs). The thesis's primary goal is to find out how the GPUs should be used for the offloading. The thesis follows the case study approach and the selected case studies are layer 2 Bloom filter forwarding and flow lookup in Openflow switch. Implementation alternatives and evaluation methodology are proposed for both of the case studies. Then, the prototype implementation for comparing between traditional CPU-only and GPU-offloading approach is developed and evaluated. The primary findings from this work are criteria of network processing functions suitable for GPU offloading and tradeoffs involved. The criteria are no inter-packet dependency, similar processing flows for all packets, and within-packet parallel processing opportunity. This offloading trades higher latency and memory consumption for higher throughput.
Nätverksteknik ansluter fler och fler människor runt om i världen. Det har blivit en viktig del av vårt dagliga liv. För att denna anslutning skall vara sömlös, måste nätet vara snabbt. Den snabba tillväxten i nätverkstrafiken och olika kommunikationsprotokoll sätter stora krav på processorer som hanterar all trafik. Befintliga lösningar på detta problem, t.ex. ASIC, FPGA, NPU, och TOE är varken kostnadseffektivt eller lätta att hantera, eftersom de kräver speciell hårdvara och anpassade konfigurationer. Denna avhandling angriper problemet på ett annat sätt genom att avlasta nätverks processningen till grafikprocessorer som sitter i vanliga pc-grafikkort. Avhandlingen främsta mål är att ta reda på hur GPU bör användas för detta. Avhandlingen följer fallstudie modell och de valda fallen är lager 2 Bloom filter forwardering och ``flow lookup'' i Openflow switch. Implementerings alternativ och utvärderingsmetodik föreslås för både fallstudierna. Sedan utvecklas och utvärderas en prototyp för att jämföra mellan traditionell CPU- och GPU-offload. Det primära resultatet från detta arbete utgör kriterier för nätvärksprocessfunktioner lämpade för GPU offload och vilka kompromisser som måste göras. Kriterier är inget inter-paket beroende, liknande processflöde för alla paket. och möjlighet att köra fler processer på ett paket paralellt. GPU offloading ger ökad fördröjning och minneskonsumption till förmån för högre troughput.

The Global Position System (GPS) has become nearly mandatory in our daily life,like the Internet. Since it (the part for civilian use) is free, open and accurate,lots of applications have made our life more convenient and more effective, suchas the location-based applications for cell phones, tracking bulldozers, shippingcontainers, etc. GPS is becoming mature and rather accurate, but its securitycan’t be neglected since it is widely used in the world. RF interference can beclassified into: intentional and unintentional interference. There are lots of RF inour surroundings, whose frequency might be close to GPS frequency, could affectthe GPS accuracy, or even sometimes make it unavailable. This project, I analyzetwo types interferences, spoofing and jamming interference. I implement two attacks:a version of Cicada attack, to check how this specific attack affects GPS, and thedistance-deceasing attack, a special type of a relay attack (Early Detect(ED) attackand Late Commit(LC) attack). I find (i) that the Cicada attack, as implemented,is essentially equivalent to jamming, and (ii) how to set up the ED/LC attacks tosucceed (i.e., have low BER).