In some fields of biometrical research joint modelling of longitudinal measures and event time data has become very popular. This article reviews the work in that area of recent fruitful research by classifying approaches on joint models in three categories: approaches with focus on serial trends, approaches with focus on event time data and approaches with equal focus on both outcomes. Typically longitudinal measures and event time data are modelled jointly by introducing shared random effects or by considering conditional distributions together with marginal distributions. We present the approaches in an uniform nomenclature, comment on sub-models applied to longitudinal measures and event time data outcomes individually and exemplify applications in biometrical research.
loss of isocyanate followed by a four-to a five-membered ring expansion upon insertion of CO. The detailed mechanism of formation of 3 (as well as 2) from aryl isocyanate and Pdo is not evident, although decarbonylation of the 7-membered palladacycle 5, formed by the head to tail coupling of three isocyanates and Pd', is probably the last step. Note. however. that a classical coupling process of two C,H,NCO ligands on Pd' to form a five-membered palladacycle such 2. followed by a further insertion of isocyanate to give 5. can be excluded since 2 does not react with isocyanate.Although the above reactions are not directly implicated in the catalytic carbonylation of nitrobenzene [']. the pervasiveness and stability of the palladacycles 1-4 and their interconversions would offer credence to the intermediacy of analogous cycles in this catalytic process, particularly if the isoelectronic and isolobal nature of certain entities involved. e.g. RNCO and CO,. are considered."" Furthermore, considering the relationship of 2 and 3 to diphenylurea and triphenylbiuret. which are undesirable by-products'21 in the carbonylation process, our results indicate that such metallacycles, however, may indeed play a subsidiary perhaps even detrimental, role in this catalytic reaction. Finally the formation of both l and 2 under the catalytic conditions described above in the absence of a proton source or alcohol would seem to argue against the existence of intermediates such as aniline in the formation of cdrbamates in this palladium
und Mnnfied t;: Rnjewsky Mutagene und cancerogene Stoffe entstammen entweder der Umwelt (einschliefllich der Nahrung) oder entstehen endogen im Organismus"]. Solche Verbindungen verursachen Strukturinodifikationen in der Desoxyribonucleinsiure (DNA) exponierter Zellen, wobei haufig kovalente DNA-Basenaddukte" -*I entstehen. Von besonderer Bedeutung ist hier die Klasse der alkylierenden Agentien, zu der viele N-Nitrosoverbindungen[2s ' * 61, polycyclische Kohlenwassers t~f f e [~] , einige Pilzmetabolite[*l und mehrere Chemotherapeutika''' gehoren. Unter den reaktiven funktionellen Gruppen der DNA gegeniiber Alkylierungsmitteln nimmt das nucleophile N-3-Atom des Desoxyadenosins eine besondere Stellung ein, da seine Alkylierung eine Destabilisierung der N-glycosidischen Bindung b e~i r k t [~] , in deren Folge es zur Freisetzung von N-3-substituierten Adeninen und zur Ausbildung von Apurin-Stellen (,,abasic sites") in der DNA kommt , Zusdtzlich werden 3-Alkyladenine durch DNA-Reparaturenzyme (3-Alkyladenin-DNA-Glycosylase) aus der DNA entferntr"]. Viele modifizierte Basen werden nicht weiter metabolisiert und gelangen so unverandert in Korperfliissigkeiten (Urin, Blutplasmd)["l. Neben der DNA ist auch die RNA ein potentielles Ziel alkylierender Verbindungen; ausgeschiedene alkylierte Basen staminen jedoch zum 0044-8249/93/1111-17/0 S 10.00+ ,2510 Airgew. Cltenr. 1993, 105, Nr. / I
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