99 research outputs found
Novel mode of defective neural tube closure in the Non-Obese Diabetic (NOD) mouse strain
Failure to close the neural tube results in birth defects, with severity ranging from spina bifida to lethal anencephaly. Few genetic risk factors for neural tube defects are known in humans, highlighting the critical role of environmental risk factors, such as maternal diabetes. Yet, it is not well understood how altered maternal metabolism interferes with embryonic development, and with neurulation in particular. We present evidence from two independent mouse models of diabetic pregnancy that identifies impaired migration of nascent mesodermal cells in the primitive streak as the morphogenetic basis underlying the pathogenesis of neural tube defects. We conclude that perturbed gastrulation not only explains the neurulation defects, but also provides a unifying etiology for the broad spectrum of congenital malformations in diabetic pregnancies
Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin
We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected]
Towards reconciling structure and function in the nuclear pore complex
The spatial separation between the cytoplasm and the cell nucleus necessitates the continuous exchange of macromolecular cargo across the double-membraned nuclear envelope. Being the only passageway in and out of the nucleus, the nuclear pore complex (NPC) has the principal function of regulating the high throughput of nucleocytoplasmic transport in a highly selective manner so as to maintain cellular order and function. Here, we present a retrospective review of the evidence that has led to the current understanding of both NPC structure and function. Looking towards the future, we contemplate on how various outstanding effects and nanoscopic characteristics ought to be addressed, with the goal of reconciling structure and function into a single unified picture of the NPC
Cationic polyelectrolytes: A new look at their possible roles as opsonins, as stimulators of respiratory burst in leukocytes, in bacteriolysis, and as modulators of immune-complex diseases (A review hypothesis)
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44497/1/10753_2004_Article_BF00915991.pd
Scanning tunneling microscopy of hydrogenated amorphous silicon : high-resolution topography and local apparent barrier heights
Bestrahlungsexperimente mit Thermionischen Brennelementen in der Kernforschungsanlage Jülich
Im Rahmen des ITR-Projektes wurden zwei Bestrahlungsexperimente mit thermionischen Brennelementen (Dreifachdioden) durchgeführt. Dabei ergaben sich Bestrahlungszeiten von 1545 bzw. 1466 Stunden bei einer durchschnittlichen Leistung von 32 W/cm Emitteroberfläche. Nach einer kurzen Beschreibung der Experimentiereinrichtung werden die Zeitverläufe der wesentlichen Parameter und die beim zweiten Experiment aufgenommenen Strom-Spannungs-Kennlinien dargestellt. Die Experimente mußten aus Sicherheitsgründen abgebrochen werden, da Lecks der Spaltgasräume auftraten. Zur Beurteilung des technologischen Stands der Brennelemententwicklung sind künftig mehr quantitative Aussagen über die Intensität und den Einfluß der thermischen Wechselbelastungen erforderlich. Zur Zeit kann nur vermutet werden, daß sie bei den Bestrahlungsexperimenten im Vergleich zum voraussichtlichen Anwendungsfall stark sind
Der Einfluß der Wandmaterialien auf die Ablagerung von Cs in HTR-Kühlkreisläufen
Es werden grundsätzliche Vorstellungen zum Einfluß des Wandmaterials auf die Spaltproduktablagerung in Hochtemperaturreaktor(HTR) -Kühlkreisläufen entwickelt, die die Mechanismen Adsorption, Löslichkeit und Diffusion einschließen. Allgemeine Gesetzmäßigkeiten der Cs-Adsorption auf technischen Metallen werden anhand experimenteller Daten aus der Literatur dargestelltund diskutiert. Aus Messungen der Elektronenaustrittsarbeit von Metallen in Cs-Atmosphäre von R.G. W i I s o n werden unter Verwendung dieser Gesetzmäßigkeiten Desorptionsenergien und Frequenzfaktoren bestimmt. Die Löslichkeiten und die Diffusionskonstanten von Cs sind in den wenigen untersuchten Fällen (Mo, Ta) so klein, daß "high diffusivity paths" in Betracht gezogen werden müssen. Thermochemische Überlegungen zum Einfluß von gasförmigen Verunreinigungen auf das Ablagerungsverhalten leiden unter dem Mangel an verlässliehen Daten
Characterization of the surfaces of hydrogen-passivated silicon by STM
Hydrogen-passivated silicon (amorphous, microcrystalline or crystalline silicon) is characterized by a low density of surface states. Thus, standard tunnelling theory, which relies on tunnelling at the Fermi energy, may not be applicable to this class of materials and it may be difficult to optimize scanning tunnelling microscopy. We performed simultaneous measurements of topography (by constant-current imaging) and of the distribution of the local apparent barrier height, phi(A), as a function of the tunnelling voltage on hydrogen-passivated, misoriented Si(111) samples that were prepared by etching with NH4F solution. Tunnelling conditions were identified, which allow the characterization of inhomogeneities related to both local roughness and chemical composition. (C) 2000 Elsevier Science S.A. All rights reserved
Eindiffusion von Cs in Hochtemperaturlegierungen (Eine Untersuchung mittels Raster - Augerelektronen - Spektroskopie und Sekundärionen-Massenspektrometrie)
Proben von Hochtemperaturlegierungen (TZM, Nimocast) sowie je ein Mo- und ein Ni-Einkristall wurden für 509 Stunden bei 78O°C in Cs-Dampf von 7 x 10 Torr geglüht. Anschließend wurden Cs-Konzentrationsprofile senkrecht zur Oberfläche mittels Raster-Augerelektronen-Spektroskopie und Sekundärionen-Massenspektrometrie in Verbindung mit Ar-Ionenzerstäubung bestimmt. Für eineCs-Konzentration von 0,1 Atomprozent ist die Eindringtiefe bei Mo (110) etwa 100 , bei TZM etwa 300 , bei Ni (110) etwa 1000 und bei Nimocast in der Größenordnung von 1m
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