124 resultados para U1 Snrnp
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Pós-graduação em Odontologia - FOA
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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No presente trabalho estudamos a existência e unicidade de solução bem como o decaimento exponencial do modelo abaixo. Nosso resultado mais importante versa sobre o decaimento exponencial do sistema termo-elástico-poroso: Cattaneo versus Fourier, dado por: ρutt = µuxx + bφx − βθx em (0, π) × (0, ∞), Jθφtt = αφxx − bux − ξφ+mθ – γφt em (0, π) × (0, ∞), cθt = k∗qx − βuxt − mφt em (0, π) × (0, ∞), τq mφt= −βq − θx em (0, π) × (0, ∞), u = φx = θ = q = 0 sobre (0, π) × (0, ∞), (u(., 0), φ (., 0), θ (., 0), q(., 0)) = (u0 (x), φ0 (x), θ0 (x), q0 (x)) em (0, π), (ut(., 0), φt(., 0)) = (u1(x), φ1(x)) em (0, π), a existência e unicidade sera´ obtida usando o Teorema de Lumer-Phillips e para o decaimento exponencial usaremos uma técnica de semigrupo.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The Columbia Channel (CCS) system is a depositional system located in the South Brazilian Basin, south of the Vitoria-Trindade volcanic chain. It lies in a WNW-ESE direction on the continental rise and abyssal plain, at a depth of between 4200 and 5200 m. It is formed by two depocenters elongated respectively south and north of the channel that show different sediment patterns. The area is swept by a deep western boundary current formed by AABW. The system has been previously interpreted has a mixed turbidite-contourite system. More detailed study of seismic data permits a more precise definition of the modern channel morphology, the system stratigraphy as well as the sedimentary processes and control. The modern CCS presents active erosion and/or transport along the channel. The ancient Oligo-Neogene system overlies a ""upper Cretaceous-Paleogene"" sedimentary substratum (Unit U1) bounded at the top by a major erosive ""late Eocene-early Oligocene"" discordance (D2). This ancient system is subdivided into 2 seismic units (U2 and U3). The thick basal U2 unit constitutes the larger part of the system. It consists of three subunits bounded by unconformities: D3 (""Oligocene-Miocene boundary""), D4 (""late Miocene"") and D5 (""late Pliocene""). The subunits have a fairly tabular geometry in the shallow NW depocenter associated with predominant turbidite deposits. They present a mounded shape in the deep NE depocenter, and are interpreted as forming a contourite drift. South of the channel, the deposits are interpreted as a contourite sheet drift. The surficial U3 unit forms a thin carpet of deposits. The beginning of the channel occurs at the end of U1 and during the formation of D2. Its location seems to have been determined by active faults. The channel has been active throughout the late Oligocene and Neogene and its depth increased continuously as a consequence of erosion of the channel floor and deposit aggradation along its margins. Such a mixed turbidite-contourite system (or fan drift) is characterized by frequent, rapid lateral facies variations and by unconformities that cross the whole system and are associated with increased AABW circulation. (C) 2009 Elsevier B.V. All rights reserved.
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[EN]Many different complex systems depend on a large number n of mutually independent random Boolean variables. The most useful representation for these systems –usually called complex stochastic Boolean systems (CSBSs)– is the intrinsic order graph. This is a directed graph on 2n vertices, corresponding to the 2n binary n-tuples (u1, . . . , un) ∈ {0, 1} n of 0s and 1s. In this paper, different duality properties of the intrinsic order graph are rigorously analyzed in detail. The results can be applied to many CSBSs arising from any scientific, technical or social area…
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Sono indagate le implicazioni teoriche e sperimentali derivanti dall'assunzione, nella teoria della relatività speciale, di un criterio di sincronizzazione (detta assoluta) diverso da quello standard. La scelta della sincronizzazione assoluta è giustificata da alcune considerazioni di carattere epistemologico sullo status di fenomeni quali la contrazione delle lunghezze e la dilatazione del tempo. Oltre che a fornire una diversa interpretazione, la sincronizzazione assoluta rappresenta una estensione del campo di applicazione della relatività speciale in quanto può essere attuata anche in sistemi di riferimento accelerati. Questa estensione consente di trattare in maniera unitaria i fenomeni sia in sistemi di riferimento inerziali che accelerati. L'introduzione della sincronizzazione assoluta implica una modifica delle trasformazioni di Lorentz. Una caratteristica di queste nuove trasformazioni (dette inerziali) è che la trasformazione del tempo è indipendente dalle coordinate spaziali. Le trasformazioni inerziali sono ottenute nel caso generale tra due sistemi di riferimento aventi velocità (assolute) u1 e u2 comunque orientate. Viene mostrato che le trasformazioni inerziali possono formare un gruppo pur di prendere in considerazione anche riferimenti non fisicamente realizzabili perché superluminali. È analizzato il moto rigido secondo Born di un corpo esteso considerando la sincronizzazione assoluta. Sulla base delle trasformazioni inerziali si derivano le trasformazioni per i campi elettromagnetici e le equazioni di questi campi (che sostituiscono le equazioni di Maxwell). Si mostra che queste equazioni contengono soluzioni in assenza di cariche che si propagano nello spazio come onde generalmente anisotrope in accordo con quanto previsto dalle trasformazioni inerziali. L'applicazione di questa teoria elettromagnetica a sistemi accelerati mostra l'esistenza di fenomeni mai osservati che, pur non essendo in contraddizione con la relatività standard, ne forzano l'interpretazione. Viene proposto e descritto un esperimento in cui uno di questi fenomeni è misurabile.
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Metastasierender Krebs ist bei Erwachsenen in der Regel nicht heilbar. Eine Ausnahme stellen testikuläre Keimzelltumoren (TKZT) dar, da über 75 % der Patienten mit fortgeschrittenen metastasierenden TKZT mit einer auf Cisplatin basierenden Kombinations-Chemotherapie geheilt werden können. Zelllinien, die aus TKZT isoliert wurden, behalten diese Cisplatin-Sensitivität in vitro bei. Somit spiegeln Testistumorzelllinien die klinische Situation wider und sind deswegen ein gutes Modellsystem um zu untersuchen, welche Faktoren der Cisplatin-Sensitivität zugrunde liegen. Die Ursachen der Cisplatin-Sensitivität in Testistumoren sind nicht bekannt. Es wurde bereits gezeigt, dass Testistumorzellen eine geringe Kapazität für die Entfernung von Cisplatin-induzierten DNA-Platinierungen aufweisen. Dieser Defekt in der DNA-Reparatur könnte ein Faktor für die beobachtete Cisplatin-Sensitivität sein. Cisplatin induziert sowohl Intrastrang-Vernetzungen als auch Interstrang-Vernetzungen (ICLs). Die Bildung und Reparatur der Cisplatin-induzierten Intrastrang-Vernetzungen wurde mittels DNA-Slot-Blot, die Bildung und Entfernung von Interstrang-Vernetzungen wurde mithilfe des Comet-Assays untersucht. In der vorliegenden Arbeit wurde gezeigt, dass die Reparatur von Intrastrang-Vernetzungen in Testis- und Blasentumorzelllinien vergleichbar ist. Somit sind Testistumorzellen in diesem Reparaturweg nicht beeinträchtigt. Im Unterschied dazu zeigte sich, dass Testistumorzellen die ICLs nicht oder nur mit einer reduzierten Kapazität entfernen können.Da die ICL-Reparatur über die Bildung von DNA-Doppelstrangbrüchen (DSB) mit anschließender DSB-Reparatur verläuft, wurde die Kinetik der DSB-Reparatur anhand der Immundetektion der Histon-Variante γH2AX, die zur Visualisierung von DSB verwendet wird, verfolgt. γH2AX Foci wurden nach Behandlung mit Cisplatin in Testistumorzellen und Blasentumorzellen gebildet. Anders als in Blasentumorzellen blieb der Prozentsatz an γH2AX-positiven Zellen in Testistumorzellen bestehen. Offensichtlich konnten die Testistumorzellen die Cisplatin-induzierten ICLs nicht korrekt prozessieren, was dazu führte, dass γH2AX Foci persistierten. Da unreparierte DNA-Läsionen eine DNA-schadensabhängige Antwort einleiten können, wurde die Aktivierung der Hauptfaktoren dieser Signalwege untersucht. In den Testistumorzellen zeigte sich eine Erhöhung der p53 Proteinmenge nach Cisplatin-Behandlung. Des Weiteren wurde die durch Cisplatin induzierte Aktivierung von ATM/ATR, Chk1/Chk2, Bax und Noxa in Testis- und Blasentumorzellen vergleichend untersucht. Es wurde bereits gezeigt, dass der Reparaturfaktor ERCC1-XPF in Testistumorzelllinien reduziert vorliegt. Um eine mögliche Rolle von ERCC1-XPF für die Reparatur-Defizienz der ICLs und Cisplatin-Sensitivität in Testistumorzellen zu analysieren, wurde ERCC1-XPF in der Testistumorenzelllinie 833K mithilfe eines Expressionsvektors überexprimiert, und der Einfluss von ERCC1-XPF auf ICL-Reparatur sowie Cisplatin-Sensitivität wurde ermittelt. Überexpression von ERCC1-XPF führte zur Reparatur der ICLs in 833K-Zellen und verminderte die Cisplatinsensitivität. Somit scheint die Cisplatinsensitivität der Testistumorzellen, zumindest zum Teil, auf einer verminderten ICL-Reparatur zu beruhen. Des Weiteren wurde in „proof of principle“ Experimenten ERCC1-XPF in der Cisplatin-resistenten Blasentumorzelllinie MGH-U1 mittels siRNA herunterreguliert, und die Auswirkung der Herunterregulation auf die ICL-Reparatur und die Cisplatinsensitivität wurde geprüft. RNA-Interferenz-vermittelte Herunterregulierung von ERCC1-XPF reduzierte die Prozessierung der Cisplatin-induzierten ICLs und verstärkte die Cisplatinsensitivität in MGH-U1 Zellen. Somit wurde in dieser Arbeit zum ersten Mal gezeigt, dass die Testistumorzellen in Vergleich zu Blasentumorzellen in der Reparatur von ICLs defizient sind, wobei die verminderte ICL-Reparatur auf die geringe Expression von ERCC1-XPF zurückgeführt werden konnte. Diese ICL-Reparatur-Defizienz könnte, zumindest zu einem Teil, für die Sensitivität der Testistumoren gegenüber Cisplatin verantwortlich sein.
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Spinal muscular atrophy (SMA) is a lethal hereditary disease caused by homozygous deletion/inactivation of the survival of motoneuron 1 (SMN1) gene. The nearby SMN2 gene, despite its identical coding capacity, is only an incomplete substitute, because a single nucleotide difference impairs the inclusion of its seventh exon in the messenger RNA (mRNA). This splicing defect can be corrected (transiently) by specially designed oligonucleotides. Here we have developed a more permanent correction strategy based on bifunctional U7 small nuclear RNAs (snRNAs). These carry both an antisense sequence that allows specific binding to exon 7 and a splicing enhancer sequence that will improve the recognition of the targeted exon. When expression cassettes for these RNAs are stably introduced into cells, the U7 snRNAs become incorporated into small nuclear ribonucleoprotein (snRNP) particles that will induce a durable splicing correction. We have optimized this strategy to the point that virtually all SMN2 pre-mRNA becomes correctly spliced. In fibroblasts from an SMA patient, this approach induces a prolonged restoration of SMN protein and ensures its correct localization to discrete nuclear foci (gems).
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Uridine-rich small nuclear (U snRNAs), with the exception of the U6 snRNA, are RNA polymerase II (RNAPII) transcripts. The mechanism of 3’ cleavage of snRNAs has been unknown until recently. This area was greatly advanced when 12 of the Integrator complex subunits (IntS) were purified in 2005 through their interaction with the C-terminal domain (CTD) of the large subunit (RpbI) of RNAPII. Subsequently, our lab performed a genome-wide RNAi screen that identified two more members of the complex that we have termed IntS13 and IntS14. We have determined that IntS9 and 11 mediate the 3’ cleavage of snRNAs, but the exact function of the other subunits remains unknown. However, through the use of a U7 snRNA-GFP reporter and RNAi knockdown of the Integrator subunits in Drosophila S2 cells, we have shown that all subunits are required for the proper processing of snRNAs, albeit to differing degrees. Because snRNA transcription takes place in the nucleus of the cell, it is expected that all of the Integrator subunits would exhibit nuclear localization, but the knowledge of discrete subnuclear localization (i.e. to Cajal bodies) of any of the subunits could provide important clues to the function of that subunit. In this study, we used a cell biological approach to determine the localization of the 14 Integrator subunits. We hypothesized that the majority of the subunits would be nuclear, however, a few would display distinct localization to the Cajal bodies, as this is where snRNA genes are localized and transcribed. The specific aims and results are: 1. To determine the subcellular localization of the 14 Integrator subunits. To accomplish this, mCherry and GFP tagged clones were generated for each of the 14 Drosophila and human Integrator subunits. Confocal microscopy studies revealed that the majority of the subunits were diffuse in the nucleus, however, IntS3 formed discrete subnuclear foci. Surprisingly, two of the subunits, IntS2 and 7 were observed in cytoplasmic foci. 2. To further characterize Integrator subunits with unique subcellular localizations. Colocalization studies with endogenous IntS3 and Cajal body marker, coilin, showed that these two proteins overlap, and from this we concluded that IntS3 localized to Cajal bodies. Additionally, colocalization studies with mCherry-tagged IntS2 and 7 and the P body marker, Dcp1, revealed that these proteins colocalize as well. IntS7, however, is more stable in cytoplasmic foci than Dcp1. It was also shown through RNAi knockdown of Integrator subunits, that the cytoplasmic localization of IntS2 and 7 is dependent on the expression of IntS1 and 11 in S2 cells.