32 research outputs found

    Prognose der Anzahl von Pareto-optimalen Lösungen für bikriterielles Facility Location Problem

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    Die Grundidee dieser Arbeit liegt darin, dass ein einfaches bikriterielles Facility Location Problem zugrundegelegt wird. Es kann sich zum Beispiel um ein Standortauswahl-Problem handeln. Bei Standortauswahl-Problem können verschiedene Kriterien eine Rolle spielen. In dieser Arbeit werden zwei Kriterien ausgewählt. Einerseits wird ein Kostenkriterium anderseits Coverage-Kriterium gewählt. Weiter wird anhand einer kleinen Stichprobe von Näherungslösungen die Anzahl der Pareto-Optima der gesamten Lösungsmenge vorhersagt. Das geschieht in folgenden vier Schritten. Zuerst werden mit Hilfe von lokaler Suche unter zufälligen Chebyshev-Gewichtsvektoren die lokalen Pareto-Minima bestimmt. Danach wird die Anzahl aller lokalen Pareto- Minima mit Hilfe der Rückfangmethode geschätzt. Im nächsten Schritt wird für die lokalen Pareto-Minima eine Dichtefunktion geschätzt (Kernschätzer-Technik). Als Kernschätzer kann man einen zweidimensionalen Gaussian Kernel verwenden. Zuletzt werden Zufallspunkte aus der geschätzten Dichte gezogen und unter diesen Punkte werden globale Pareto-Minima bestimmt. Durch Mitteln über eine größere Anzahl von Versuchen erhält man einen Schätzwert für die Anzahl der globalen Pareto-Minima

    The potency of the fs260 connexin43 mutant to impair keratinocyte differentiation is distinct from other disease-linked connexin43 mutants

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    Although there are currently 62 mutants of Cx43 (connexin43) that can cause ODDD (oculodentodigital dysplasia), only two mutants have also been reported to cause palmar plantar hyperkeratosis. To determine how mutants of Cx43 can lead to this skin disease, REKs (rat epidermal keratinocytes) were engineered to express an ODDD-associated Cx43 mutant always linked to skin disease (fs260), an ODDD-linked Cx43 mutant which has been reported to sometimes cause skin disease (fs230), Cx43 mutants which cause ODDD only (G21R, G138R), a mouse Cx43 mutant linked to ODDD (G60S), a non-disease-linked truncated Cx43 mutant that is trapped in the endoplasmic reticulum (Δ244*) or full-length Cx43. When grown in organotypic cultures, of all the mutants investigated, only the fs260-expressing REKs consistently developed a thinner stratum corneum and expressed lower levels of Cx43, Cx26 and loricrin in comparison with REKs overexpressing wild-type Cx43. REKs expressing the fs260 mutant also developed a larger organotypic vital layer after acetone-induced injury and exhibited characteristics of parakeratosis. Collectively, our results suggest that the increased skin disease burden exhibited in ODDD patients harbouring the fs260 mutant is probably due to multiple additive effects cause by the mutant during epidermal differentiation

    Life-Cycle and Genome of OtV5, a Large DNA Virus of the Pelagic Marine Unicellular Green Alga Ostreococcus tauri

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    Large DNA viruses are ubiquitous, infecting diverse organisms ranging from algae to man, and have probably evolved from an ancient common ancestor. In aquatic environments, such algal viruses control blooms and shape the evolution of biodiversity in phytoplankton, but little is known about their biological functions. We show that Ostreococcus tauri, the smallest known marine photosynthetic eukaryote, whose genome is completely characterized, is a host for large DNA viruses, and present an analysis of the life-cycle and 186,234 bp long linear genome of OtV5. OtV5 is a lytic phycodnavirus which unexpectedly does not degrade its host chromosomes before the host cell bursts. Analysis of its complete genome sequence confirmed that it lacks expected site-specific endonucleases, and revealed the presence of 16 genes whose predicted functions are novel to this group of viruses. OtV5 carries at least one predicted gene whose protein closely resembles its host counterpart and several other host-like sequences, suggesting that horizontal gene transfers between host and viral genomes may occur frequently on an evolutionary scale. Fifty seven percent of the 268 predicted proteins present no similarities with any known protein in Genbank, underlining the wealth of undiscovered biological diversity present in oceanic viruses, which are estimated to harbour 200Mt of carbon
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