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This paper deals with an optimization problem of determining the maintenance units and age‐based inspection schemes to minimize the expected maintenance cost rate and satisfy a target system availability for multi‐indenture systems that have a modular structure with redundant units. Failures of primary components directly lead to system failures and can therefore be identified and maintained immediately, while failures of redundant components need to be identified by inspections. And the designated maintenance units need to be replaced during maintenance. By constructing the dual structure of the fault tree, we present a failure path enumeration method, based on which the system availability and expected maintenance cost rate models considering maintenance time are derived. For redundant units, two types of inspection policies are considered in our models: one is the corrective maintenance (CM)‐based inspection policy, and the other one is the age‐based inspection (PM) policy, inspections are performed at failures or age h, depending on which occurred earlier. A heuristic algorithm is proposed to find the reasonable maintenance units and inspection intervals simultaneously, and its performance is also compared and analyzed. Several numerical examples are studied to investigate the effect of parameters on optimal solutions. [ABSTRACT FROM AUTHOR]

Principal Stratification Designs to Estimate Input Data Missing Due to Death Nous nous intéressons à des études portant sur des cohortes d'individus après la survenue d'un événement critique, comme une blessure, et ayant les caractéristiques suivantes. Premièrement, les études sont conçues pour mesurer des variables d'“input”, qui décrivent la période avant l'événement critique, et pour caractériser la distribution des variables d'“input” dans la cohorte. Deuxièmement, les études sont conçues pour mesurer des variables d'“output”, principalement la mortalité après l'événement critique et pour caractériser la distribution prédictive (conditionnelle) de la mortalité connaissant les variables d'“input” dans la cohorte. De telles études présentent souvent la complication que les données d'“input” manquent pour ceux qui meurent peu après l'événement critique car le recueil des données est réalisé après l'événement. Les méthodes standard de prise en compte des “inputs” manquants, telles que les méthodes d'imputation ou de pondération basées sur l'hypothèse que l'on peut ignorer le processus de données manquantes, sont connues comme étant en général non valides quand le processus de données manquantes ne peut être ignoré, c'est à dire quand la distribution des “inputs” est différente chez ceux qui meurent et ceux qui survivent. Pour répondre à ce problème, nous proposons un nouveau schéma qui recueille et utilise l'information sur une autre variable importante—un traitement ou une variable sous contrôle externe, qui, si elle avait étéà son niveau optimal aurait pu empêcher le décès de ceux qui sont morts. Nous montrons que ce nouveau schéma peut être utilisé pour faire des inférences valides pour la distribution marginale des “inputs” dans la cohorte entière et pour la distribution conditionnelle de la mortalité connaissant les “inputs”, également dans la cohorte entière, même si le processus de données manquante ne peut être ignoré. Le contexte crucial que nous utilisons est la stratification principale basée sur les “outputs” potentiels, comme ici la mortalité après les deux niveaux de traitement. Nous montrons aussi à l'aide de données préliminaires sur des blessures, que notre approche peut donner des résultats qui sont plus raisonnables que les résultats obtenus par les méthodes standard, et ceci de façon relativement dramatique. Ainsi notre approche suggère que le recueil en routine de données sur des variables qui pourraient être utilisées comme traitement possible dans de telles études d'“inputs” et de mortalité devrait être fait en routine. [ABSTRACT FROM AUTHOR]

645 La biologie informatique est un domaine d'évolution rapide, dans lequel les méthodologies provenant de l'informatique, des mathématiques et des statistiques sont appliquées pour traiter les problèmes fondamentaux de la biologie. L'étude de l'information de régulation des gènes est un problème au centre de l'informatique biologique. Cet article rassemble les développements récents de méthodes statistiques liées à ce thème. Partant de la sélection de puces génétiques, nous examinons les méthodes de recherche des éléments de liaison et des modules cis-régulés des facteurs de transcription dans les gènes co-régulés, ainsi que les méthodes pour l'utilisation de l'information des comparaisons croisant les espèces et des expériences ChIP-chip. La meilleure compréhension de la logique de cis-régulation dans le génôme des mammifères peut nécessiter l'information provenant de ces étapes. 691 Les modèles de capture-recapture ont été développés pour estimer la survie à partir de données provenant du marquage et de la surveillance d'animaux sauvages dans le temps. Les différences de survie peuvent être expliquées en incluant des covariables appropriées. Nous proposons des méthodes de régression non-paramétrique et semi-paramétrique pour estimer la survie dans les modèles de capture-recapture. Une approche totalement bayésienne utilisant des simulations MCMC est utilisée pour estimer les paramètres du modèle. Ce travail est illustré par une étude de Pétrels des neiges, dans laquelle les probabilités de survie sont exprimées comme fonctions non-linéaires d'une covariable de climat, en utilisant des données d'une étude de 40 ans d'observation sur des animaux marqués, nichant sur l'île des Pétrels en Terre Adélie. [ABSTRACT FROM AUTHOR]

664 Les plans adaptatifs permettent, en cours d'étude, de modifier le plan d'expérience initial de façon importante. La taille de l'échantillon, en particulier, peut être réévaluée au vu de données intermédiaires ou d'informations extérieures à l'essai. Dans les plans adaptatifs standard, on associe ces modifications à un test pondéré qui garantit le contrôle de l'erreur de première espèce. Cette méthode, cependant, viole des principes de base de la statistique inférentielle. C'est ainsi que, dans un exemple portant sur des données indépendantes issues de la loi normale N(μ, 1), un test adaptatif peut rejeter l'hypothèse nulle μ≤ 0, alors même que la moyenne des observations est négative. Nous en concluons que les plans adaptatifs, au moins dans leur forme la plus générale où l'on recourt à un test pondéré, ne sont pas valides. Nous discutons plusieurs modifications possibles de cette méthodologie des plans adaptatifs, en nous concentrant sur la recherche de solutions satisfaisantes quant aux tests d'hypothèses. [ABSTRACT FROM AUTHOR]

The paper empirically analyzes the financial development (FD)-growth nexus, and the financial development-total factor productivity (TFP) link in sub-Saharan Africa. The study is based on a VAR approach: Johansen cointegration tests and error correction models. The sample includes 22 countries over the period from 1960 to 2002. Results suggest that FD and economic growth and, FD and TFP are cointegrated for many countries. Moreover, in many cases, the relationship between FD and growth is characterized by bidirectional causality in the Granger sense, whereas the relation between FD and TFP is characterized by a unidirectional causality running from FD to TFP. With few exceptions, it appears that financial development spurs economic growth in countries where that growth is supported by technological progress. The implication of the findings is that any reform that causes betterment in the financial sector will foster economic growth through a sharp increase in technological progress. [ABSTRACT FROM AUTHOR]

Résumé: Alors qu'après une longue période de stagnation la croissance semble être revenue en Afrique, la question se pose de savoir si la nouvelle croissance africaine est durable. Cet article examine dans quelle mesure la croissance africaine est vulnérable aux chocs exogènes et quelles en sont les implications pour le financement internatìonal du développement. It montre en premier lieu la persistance de la vulnérabilité des économies africaines au regard de l'indice de vulnérabilitééconomique des Nations unies (EVI), utilisant une première série rétrospective de cet indice. En second lieu, s'appuyant sur divers travaux récents, il souligne l'importance de la vulnérabilité structurelle pour la croissance et le développement, particullèrement en Afrique. Enfin il examine le rôle du financement international pour réspondre à la vulnérabilité des économies africaines, suggérant de faire de la vulnérabilité structurelle un des critères d'allocation de l'aide de d'adapter les modailités de l'aide pour lui faire jouer de façon efficace un rôle d'assurance. While after a long stagnation growth seems to have come back in Africa, the issue remains to know whether the new African growth is sustainable. This paper examines to what extent African growth is vulnerable to exogeneous shocks and what are the implications for international developement finance. First it evidences the persistent vulnerability of African economies with regard to the U.N. Economic Vulnerability Index (EVI), using a first retrospective series of that index. Second, relying on several recent works, it unerlines that structural vulnerability matters, in particular in Africa. Finally it considers how international development finance can be used to face the vulnerability of African economies, suggesting to use structural vulnerability as one of the aid allocation criteria and to adopt modalities of aid so that it can effectively serve as an insurance. [ABSTRACT FROM AUTHOR]

R. L. Prentice, M. Pettinger, and G. L. Anderson 899 Statistical Issues Arising in the Women's Health Initiative Nous proposons un bref panorama du plan de l’essai clinique et de l’étude observationnelle de la WHI, ainsi qu’un résumé des résultats obtenus à partir de la partie de l’essai clinique dévolue à la thérapeutique hormonale post-ménopause. Depuis son démarrage en 1992, la WHI a été confrontée à plusieurs questions de nature statistique pour lesquelles de plus amples développements méthodologiques étaient nécessaires. Parmi ceux-ci, la modélisation des erreurs de mesure, et des méthodes d’analyse pour l’évaluation de la diététique et de l’activité physique; des méthodes de surveillance d’essai clinique lorsque les traitements peuvent concerner plusieurs champs cliniques aussi bien en bénéfice qu’en réaction adverse; le plan d’étude et les procédures d’analyse pour des données génomiques et protéiques de dimension élevée; et aussi des procédures d’analyse de données de durée lorsque les rapports de risque dépendent du temps. Ce dernier point apparaît important pour comprendre les différences entre les résultats de l’essai clinique et ceux de l’étude observationnelle en ce qui concerne le traitement hormonal postménopause et la pathologie cardio-vasculaire. [ABSTRACT FROM AUTHOR]

The complexes of poly A and poly U are interesting models for studying the structure of nucleic acids. In the first part of this paper, the thermal stability of these complexes has been studied as a function of both pH and ionic strength in alkaline solution. The thermal stability is measured by the half transition temperatures, or Tm's. There are four different kinds of transitions: Tm2-1 refers to the dissociation of the two-stranded complex, poly (A + U); Tm2-1 to the dissociation of the three-stranded complex, poly (A + 2U) [4]. Tm8-2 is the temperature of half dissociation of poly (A + 2U) into poly (A + U) [1], and Tm2-3 is the temperature of rearrangement of 2 poly (A + U) into poly (A + 2U) [3] (Fig. 1). It is found that Tm2-1, and Tm8-1 decrease as pH increases above neutrality (Fig. 2 and 3), but that Tm2-8 does not vary (Fig. 3). This effect is readily explained if it is assumed that the ionisation of uracil brings a change in the state of the free poly U, but that the complexes themselves are not modified. In the second part of the paper a simple thermodynamic formulation is given which represents satisfactorily the relationship between the four equilibria, as observed at neutral pH (Fig. 1). A more complex treatment is then presented. It includes quantitation of electrostatic interactions, according to the theory of Kotin [18] and of the free enthalpy term corresponding to the organisation (stacking) of poly A. This leads to an excellent representation of the experimental data (Fig. 5). In alkaline solution, one can calculate the free enthalpy change associated with the ionisation of poly U at the Tm. According to our observations, it is likely that this is the only factor responsible for the decrease of Tm. Therefore, we can write that the sum of the free enthalpy of complex formation in the same conditions, but at pH 7, and of the free enthalpy of ionisation is zero. This leads to a determination of ΔG both as a function of temperature and ionic strength: the variation of ΔG with these factors is shown to be in good agreement with our detailed model. However, the absolute values are different, probably because of uncertainties concerning the data for poly A stacking enthalpy and entropy. Apart from providing evaluation of the thermodynamic parameters for double and triple helix formation, our results lead us to emphasize the importance of the thermodynamic state of the unassociated polynucleotides. This may be particularly relevant when one considers the partially complementary secondary structures of RNA's. [ABSTRACT FROM AUTHOR]

The Action Plan for Official Languages launched in 2003 intends to revitalize the country's linguistic duality. Among the priority areas, health is the focus in order to ensure the training of health professionals to serve official language minority communities and to network the main actors concerned about the organization of services in the minority language. The aim of this paper is to report representations of Francophones in minority with respect to the future of health services in French. The study is based on a participatory methodology: concept mapping to identify the conceptual universe of a given problem. [ABSTRACT FROM AUTHOR]

Close to the monumental graves, numerous ancient wells, some of which reach a depth of 18 m, were found in the Nabatean site of Mad in āli . Their fascinating study was begun by the author, a well-known speleologist. It required a geomorphological and hydrological approach of the site which established the groundwater level and piezometric contours. Furthermore, research was conducted on the palaeoclimates and present-day pluviometry, which has concluded that the fall in the groundwater level since antiquity is mainly the result of modern exploitation. Since 1975 the high-yielding submerged pumps have provided intensive irrigation to the important agriculture of el Hijr, close to the Nabatean site. The wells, their construction, their shape and ancient mechanism are described in this paper. [ABSTRACT FROM AUTHOR]

Cet article porte sur la relation entre la mondialisation, l'innovation économique et la cohésion sociale au sein des coopératives forestières du Québec dans une perspective de développement régional. Depuis une quinzaine d'années, certaines coopératives forestières au Québec tentent d'innover dans leurs façons de gérer et de produire. Pour innover, ces coopératives s'inscrivent dans un processus de gouvernance avec l'ensemble des acteurs de l'industrie forestière dont l'État, la grande entreprise forestière et les communautés forestières. Cette nouvelle gouvernance semble non seulement permettre aux coopératives forestières d'innover, mais aussi de dynamiser leur capacitéà assurer la cohésion sociale au sein de leurs communautés d'appartenance. La gouvernance forestière apparaît donc comme une stratégie de développement régional pertinente pour les régions qui, comme les régions forestières, sont situées en périphérie et souvent économiquement dévitalisées. This paper explores the relation between globalization, economic innovation and social cohesion within the forest co-operatives of Québec from a regional development perspective. For about fifteen years, several forest co-operative in Québec have tried to innovate their ways of managing and producing. To innovate, these co-operatives have sought to insert themselves in a process of governance with the other actors of the forest industry such as the State, the large forest company and the forest communities. This new governance structure not only improves the capacity of these co-operatives to innovate, but also their capacity to generate social cohesion in their communities. The forest governance seems to be a pertinent strategy of development for peripheral forest regions that are often economically devitalized. [ABSTRACT FROM AUTHOR]

The cereal market of Togo was liberalized in 1987. This policy aims to improve markets' spatial integration through the development of arbitrage. The paper assesses the extent of maize market spatial integration in order to understand how it has been affected by price liberalization. The monthly retail maize prices collected on 13 markets for the period from 1980 to 2001 are considered. The results show that the impact of price liberalization on markets integration is moderate. The liberalization has not significantly improved the extent of long-run and short-run integration of maize markets. The speed of price adjustment is relatively weak for most of the markets. In order to improve market efficiency, it is suggested that the government should create a market information service (SIM) which will be entrusted in collecting and disseminating weekly cereal prices all over the country. [ABSTRACT FROM AUTHOR]

Economic segregation, or residential inequalities based on income, is a complex spatial process. It is associated with structures which arise at certain scales and which evolve in time. In this paper, we analyse the evolution of economic segregation in Montréal from 1980 to 2000. This analysis is based on household's income and on their distribution within the residential space from four scales: households, census tracts, municipalities and some radio-concentric zones. Results confirm that the spatial organisation of economic segregation is scale dependent. More precisely, local inequalities are growing more rapidly but this trend does not prevent the consolidation of metropolitan-sized clusters. Moreover, results confirm that Montréal's economic segregation follows North American trends like the growth of economic disparities (spatial or not) or the fact that the enrichment of central and ex-urban neighbourhoods is compensated by the impoverishment of inner-ring suburbs. [ABSTRACT FROM AUTHOR]

The objectives of the present paper were to determine how the fiscal balance, the level of employment and the economic growth evolved overtime in Côte d’Ivoire and to determine the direction of causality in the Granger sense between the fiscal balance, employment and growth. The data used for the study cover the period from 1976 to 2002. The empirical results suggest high positive correlation between the FDI, employment and GDP variables. A positive but weak correlation is found between the fiscal balance and growth. There is no cointegration relation between growth and the fiscal balance as well as between this later variable and the employment variable. With respect to causality, the results suggest a unidirectional causality from the fiscal balance towards growth. These results call for caution in the implementation of economic policies that focus too much on the fiscal balance to pull growth. [ABSTRACT FROM AUTHOR]

La question de la mesure du bien-être a ceci d'intéressant qu'elle oblige les géographes à pousser leur réflexion sur les modalités de l'interconnexion entre données objectives et données subjectives. Malgré le regain d'intérêt pour le concept sur la scène publique, peu d'efforts systématiques ont cependant été entrepris dans cette perspective. Notre article vise à pallier cette lacune en comparant une mesure objective de la qualité de vie de la population vieillissante de l'Outaouais (Québec) avec des données sur son bien-être obtenues par voie d'enquête. Le capital résidentiel, le capital social et le capital humain sont les trois grands facteurs du bien-être qui ont retenu l'attention. L'effet de milieu sur la relation du bien-être objectif au bien-être subjectif a été un important fil conducteur de la recherche. L'étude montre que, si les deux ensembles de mesures convergent assez bien, elles ne se superposent pas entièrement. Les mesures objectives de la contribution de l'environnement social au bien-être traduisent mal les satisfactions telles que révélées par l'enquête qui illustrent par ailleurs le besoin de tenir compte du sexe, du revenu et de la scolarité dans le bien-être perçu. [ABSTRACT FROM AUTHOR]

The objective of the present paper was to investigate Granger causality between export expansion and economic growth and draw implications for sustainable job creation strategies. Several statistical tests were undertaken (unit root, cointegration and Granger causality). The results suggest that despite the absence of cointegration between export and economic growth, there is a feedback relationship between export and economic growth. Moreover, the results also indicate no cointegration between the labour variable and export, public expenditures and economic growth variables. [ABSTRACT FROM AUTHOR]

Summary In the Democratic Republic of Congo, the re-emergence of sleeping sickness is no longer limited to rural areas. Over the course of the past decade, more and more cases have been reported from urban centres such as Kinshasa, Mbuji-mayi, Matadi and Boma. This paper presents a retrospective analysis on the region of Kinshasa over the period 1996–2000, using epidemiological surveillance, individual case files and available entomological data. There are 22 health districts in total; they were classified as urban when the population exceeded 5000 per square kilometre. The Human African Trypanosomiasis (HAT) control programme reported 2451 parasitologically confirmed new cases between 1996 and 2000, in the entire region of Kinshasa. Affected people (66%) were aged 15–49 years. Cases occurred in every health district, and 956 (39%) occurred in urban residents. Glossina captures in 1999 established the presence of Trypanosoma spp. Local HAT transmission is plausible but not proven. The high number of urban cases necessitates development of control strategies adapted to cities. [ABSTRACT FROM AUTHOR]

This paper gives an overview of the treatment of Human African Trypanosomiasis from the early 20th century until today. [ABSTRACT FROM AUTHOR]

An n‐affine manifold is a differentiable manifold endowed with an atlas whose transition functions are locally affine transformations of ℝn. The paper studies affine dynamic, that is, affine endomorphisms of affine manifolds. The main goal is to relate the dynamical viewpoint to the completeness problem. In particular, it is shown that the Markus conjecture is true when dim Aff(M,ᐁ) > dim M − 2. [ABSTRACT FROM PUBLISHER]

Subepidermal cells of thin tissue pieces with a few cell layers were capable of forming either buds, roots, (lowers or non-organogenetic callus. To determine whether this callus is able to differentiate into organs, we transferred it to media inducing either flowers, or buds, or roots. In this paper, we study the capacity of the callus to form buds. In 50% of the cases, the explants (being maintained for 1 day to 2 years in callus media) can still express the capacity to form buds. This percentage increased with increased agar concentration of the culture media. At the histological level, non-organogenetic callus is characterized by the absence of tracheid differentiation, whereas in the organogenetic callus, tracheids were induced after their transfer into a 'Bud medium' and indicate an organogenetic differentiation pattern. [ABSTRACT FROM AUTHOR]

A spectrophotometric technique after paper chromatography was found adequate for quantitatively determining chlorogenic and caffeic acids in the vegetative apical buds of Pyrus communis L., variety ‘Passe‐Crassane’, de ľOrléanais. Using this method, significant changes in these polyphenols were shown to occur both in tissue concentration and total amount per bud, in samples collected during winter 1973–1974. A close relationship between chlorogenic acid concentration and state of dormancy of excised twigs was found. [ABSTRACT FROM AUTHOR]

Presents an investigation of the sequencing of 65 amino acid residues at the carboxyl-terminus. Use of methods such as enzymic or chemical cleavages of the peptide chain; Fractionation of peptides by Sephadex or Dowex column chromatography, paper elctrophoresis or chromatography.

In the previous paper, a metabolic relationship between a cytochrome oxidase deficiency and threonine biosynthesis in Saccharomyces cerevisiae was proposed. It has been found that high concentrations of threonine or its immediate precursors L-aspartate- β-semi-aldehyde or homoserine, are able to restore cytochrome oxidase synthesis in threonine auxotrophs, grown in the presence of glucose as a carbon source. On the other hand, these strains are able to synthesize cytochrome oxidase when the carbon source is ethanol or glycerol even without an excess of threonine. The results show that this phenomenon is concerned with the regulation of cytochrome oxidase synthesis. Different hypotheses are presented to explain the possible role of threonine in this regulation. One of them stresses the possible role of a differential auxotrophy for the cytoplasmic and the mitochondrial protein synthesis systems. [ABSTRACT FROM AUTHOR]

Previous work of several laboratories has shown that the two carbon atoms C-28 and C-29 of the ethyl or ethylidene side chains of phytosterols are introduced on a C-24 unsaturated side chain by two successive C-methylation steps. A scheme, based on previous work of Nes et al. and Goodwin et al., gives the various intermediates which can be formed by stabilisation of the intermediate carbonium ion (II). It was usually thought that ethylidene compounds such as (III) were the precursors of ethyl compounds such as (VIII) and this has been proved recently in the case of poriferasterol (IX) which contained four deuterium atoms when Ochromonas malhamensis was grown in presence of [Me-²H3] methionine [8]. In the present paper it is reported that the sterol of the slime mold Dictyostelium discoideum [Δ 22-stigmasten-3-Β-ol (Xa)] contains five deuterium atoms, when extracted from D. discoideum fed on cells of a methionine-less strain of E. coli grown in presence of [Me-²H3] methionine. The unsaturated sterol (Xa) is accompanied by the saturated sterol (XIa) which was not previously found in this organism. Mass spectrometry of the pentadeuterated sterols (Xa) and (XIa) seemed to show conclusively that all five deuterium atoms are located in the ethyl side chain [11], but it was thought necessary to confirm this conclusion by a detailed analysis of the side chain; thus, the sterol (Xa) was ozonised and part of the side chain isolated as a crystalline p-phenylphenacyl ester (XIIIa). Mass spectrometry of this compound and of a synthetic non-labelled (XIllb) and the corresponding monodeuterated derivative (XTIJc) confirms that all five deuterium atoms of the Dictyostelium sterol (Xa) are in the ethyl side chain. These results exclude an ethylidene compound (such as III) as a precursor of the sterol (Xa); they do not allow us to choose between other possible routes illustrated th the scheme. Our experiments also show that there is no hydrogen shift during the second methylation step. [ABSTRACT FROM AUTHOR]

In the previous paper [1] we proposed a mechanism for the reaction of pancreatic ribonuclease with nucleotide diesters. in which the kinetic constants k+1 and k-1 + k+2 are assigned to a base catalysed step for the formation, and a proton catalysed step by the conjugate acid for the breakdown, of an enzyme stabilized intermediate. In the hydrolysis reaction of the 2′,3′- cyclic diesters the rates depend on the structure of the catalysing base, and in particular on its polarisability. in addition to this effect, we found that, in the dinucleoside phosphate series, the rates increased up to three orders of magnitude, depending on the nature of the base of the second nucleoside [4]. According to our suggested mechanism I-VI the accelerated rates could be due to (a) the second base influencing the polarisability of the catalysing system by π-electron interactions between the stacked bases. This effect should be reflected in the enthalpy term and should parallel the hypochromicity of the dinucleoside-phosphates exactly: (b) pre-ordering of the reacting atoms (C-2-oxygen, 2′-OH-group and phosphorus) by the base stacking, which would be reflected in a lowering of the activation energy in the entropy term and should only roughly parallel the hypochromicity. To differentiate between these two possibilities we prepared the diesters IX -XXXIV, determined the hypochromic effect and also the values of km and k+2 at pH 7. There is only a partial correlation between k+3 values and the hypochromic effect. The k+2 values vary with the structure of the second nucleoside and show a particular dependence upon the nature of the link between base and phosphate group. Highest values are found with adenosine and deoxyadenosine. Elongating the ribose with mercaptoethanol (XIX) or substituting the relatively rigid ribofuranose ring with flexible n-hexyl-, pentyl- or butyl-chains (XX-XXIII appreciably reduces the hypochromicities and also the k+2, values, in the case of a propyl link (XXIII, XXIV( or in the analogously structured 3′-3′-dinucleosidephosphate XXV no hypochromic effect is found and the k+2 values are as low as that of 3′-cytidylic acid benzyl ester. A second nucleoside attached to the 5′ end of a substrate (XXXIII. XXXIV) does not result in an increase of the rate of diester hydrolysis at the 3′ end though there is a normal hypochromicity. Therefore a pre-ordering of the reacting atoms (demonstrable on models) appears to be the accelerating factor. A specific interaction between the second nucleoside and the enzyme being responsible for the pre-ordering effect can be excluded by either blocking or varying all the potential interaction sites. The concept of a pre-ordering in the substrate due to bass stacking agrees with the results from measurements of the temperature dependence of k+2 and calculations of the enthalpy (ΔH≠) and entropy (Δ,S≠) term in the activation energy of this step. When diesters with an exactly analogous structure of the intermediate II such as CpA (IX) and Cp-butyladenine (XXII) are compared, the differences are found in the entropy term only. Between the first and second step substrates such as CpA and 2′3′-Cp the differences are also found in the entropy term with a small factor in the enthalpy term. From a comparison of Up- and Cp-diesters it can be seen that due to the differences in the enthalpy term the Up-diesters should react 5–10 times faster than Cp-diesters, but that due to the differences in the entropy term Cp-diesters react 20 times faster than Up-diesters.… [ABSTRACT FROM AUTHOR]